RNA Viruses IV: Oncogenic, Slow Viruses, HIV (V1) PDF

MICROBIOLOGY | TRANS 3D LE RNA IV: Oncogenic, Slow Viruses, HIV ERIC CONSTANTINE G. VALERA, MD, M...

MICROBIOLOGY | TRANS 3D LE RNA IV: Oncogenic, Slow Viruses, HIV ERIC CONSTANTINE G. VALERA, MD, MHSE | (09/27/2024) | Version 1 02 OUTLINE 🔺 I. RABIES I. Rabies III. Creutzfeldt-Jakob Disease A. Rhabdoviridae IV. Top 7 Viruses That Can B. Rabies Virus Replication Cause Cancer C. Rabies Virus Replication A. Viruses (Additional Notes) B. Bacteria D. Transmission V. From Virus To Cancer E. Pathogenesis VI. Human Papillomavirus F. Pathogenesis (Additional VII. Retrovirus Reverse Notes) Transcription G.Clinical Manifestations VIII. HIV & AIDS H. Clinical Manifestations IX. Human Immunodeficiency (Additional Notes) Virus I. Diagnosis X. Review Questions J. Diagnosis (Additional XI. References ❗ Notes) Figure 1. Rabies Virus [Youtube] K. Treatment A neurotropic virus belonging to the genus Lyssavirus, ❗ L. Treatment (Additional Rhabdoviridae family Notes) Bullet shaped, enveloped, -ssRNA virus, 180 nm M.Street vs Fixed Virus N. Risk Categorization & Anti-Rabies Prophylaxis 💬 in length, and 75 nm in width (+) membranous envelope with protruding spikes, inside the envelope is a ribonucleocapsid II. Prions A. Where Prion Proteins Go → Peplomers (spikes) are composed of trimers of the viral B. Prion Diseases glycoprotein C. Creutzfeldt-Jakob Disease → Genome: single stranded, negative sense RNA Must Lecturer Book Previous Youtube Rabies is a zoonotic infection, spreading from animals to humans. ❗️ Know 💬 📖 📋 Trans 🔺 Video It primarily affects mammals, including humans through bite or scratch of infected animals, commonly dogs or bats. SUMMARY OF ABBREVIATIONS The rabies virus is endemic all over the world, with the AIDS Acquired Immunodeficiency Syndrome exception of Australia. CJD Creutzfeldt-Jakob Disease In the US urban settings, dogs are the main transmitter but HIV Human Immunodeficiency Virus due to vaccination programs for dogs, rabies is now more LEARNING OBJECTIVES prominent in cats. Other animals include wild racoons, ✔ Describe the nature and characteristics, classification of skunks, bats, foxes, and farm animals. Rabies, Slow virus, Prions, and Oncogenic Viruses. In Latin America and Asia, unvaccinated dogs are a ✔ Identify their morbidity and mortality rates as well as their more common source. distribution in the Philippines A. RHABDOVIRIDAE ✔ Indicate the age, sex, and racial predilection of the infectious disease ✔ Discuss the microbiologic and pathogenesis & its immunologic response ✔ Explain the clinical manifestation based on microbiologic etiopathogenesis. ✔ Correlate the diagnostic markers and the corresponding diagnostic examinations ✔ Identify therapeutic interventions ✔ Correlate the mechanism of action of drugs ✔ Explain the epidemiology characteristics of Oncogenic viruses, Slow viruses and HIV and preventive interventions (including the role of passive and active immunization.) Figure 2. Rhabdoviridae [Youtube] ✔ Identify appropriate preventive health protocols and wellness programs to educate patients, families, and Rhabdoviruses are viruses that encode only five caregivers. proteins, appearing as bullet-shaped, enveloped virions with glycoprotein spikes on the surface. They have a helical nucleocapsid within the envelope that is symmetrically coiled into a cylindrical structure. The nucleocapsid is composed of one molecule of negative sense, single-stranded RNA about 12,000 bases long. LE 2 TG # 6 | R. Forones, A. Frace, J. Fuedan, A. TE | A. Frace AVPAA | M. Matias PAGE 1 of 20 TRANS 4 Galang, E. Galicia, J. Galolo VPAA | J. Magtibay MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE Even with only five proteins encoded, the virus has the → particles acquire an envelope by budding through the ability to protect itself from ribonuclease digestion and plasma membrane retain a shape that is ideal for transcription. → viral matrix protein forms inner layer of envelope B. RABIES VIRUS REPLICATION → viral glycoprotein forms outer layer (spikes) D. TRANSMISSION Most common: bite of an infected animal Non-bite exposures: direct contact with saliva of infected animal, and inhalation of virus containing aerosols in places like bat caves, organ transplant with infected tissue, ❗ or inoculations to mucosal membranes like scratches Incubation period: 20-90 days Human-to-human rabies infection is very rare (transmitted via neuronal tissue in the transplanted organs) Rabies virus has not been isolated from the blood of infected persons Figure 3. Rabies virus replication [Youtube] First, the glycoprotein spikes of the virus attach to the host cell, triggering endocytosis, where the plasma membrane of the host cell folds inward and forms a membrane-bound vesicle, called an endosome, around the virus The viral envelope fuses with the membrane of the endosome, which uncoats the virion and sends the nucleocapsid into the cytoplasm for replication. Within the cytoplasm, the virus uses a combination of its nucleocapsid-encoded enzymes and host cell machinery to transcribe viral RNA. Five mRNAs, one for each encoded protein, are produced. The virion then assembles in two phases. → First, the nucleocapsid is assembled in the cytoplasm. → Then the virion is pushed out through the cell plasma membrane in a process called budding, taking part of that membrane with it, giving the virion its envelope. → The new virion is now ready to infect another host cell. 💬 C. RABIES VIRUS REPLICATION (ADDITIONAL NOTES) Figure 5. Rabies transmission[Harrison’s] ❗locallyUpon entry into the body, the virus replicates at the site of inoculation before spreading via retrograde axonal transport Virus then ascends along peripheral nerves, eventually reaching the brain, where it causes fatal encephalitis E. PATHOGENESIS Figure 4. Rabies Virus Replication [Youtube] Rabies Replication → Glycoprotein spikes (attachment using nicotinic acetylcholine receptor) → RNA-dependent RNA polymerase → (-) ssRNA → (+) ssRNA) → monocistronic mRNAs code for the five virion proteins: nucleocapsid (N), polymerase proteins (L, P), matrix (M), and glycoprotein (G) Figure 6. Rabies pathology [Youtube] MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 2 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE Spreads to CNS via neuronal route Steps: → Virus in inoculated from the infected animal bite → Virus binds at the nicotinic Ach receptors at NMJ and enters into the muscle cell and replicates. → It prefers replication in neurons than muscles so it crosses the NMJ and enters a neuron to replicate further using dyenin receptors in the neuron cytoplasm and to travel within axons up to the peripheral nerves using retrograde transport → Virus replicates in motor neurons of the spinal cord and DRG and ascends the brain causing neuronal dysfunction, inflammation, and widespread neuronal Figure 8. Rabies clinical manifestations [Youtube] death. 💬 F. RABIES PATHOGENESIS (ADDITIONAL NOTES) → Virus inoculation and replication in the muscle is in the incubation phase, and typically no symptoms are in this Susceptibility to infection and incubation period phase. Incubation can last from days to months depend on: (20-90 days), to even a year. This is dependent on the → host's age location of the wound and viral load. → genetic background → Once the virus has reached the brain, the prodromal → immune status phase begins. The prodromal phase is characterized → viral strain involved by non-specific symptoms such as fever, malaise, → amount of inoculum headache, and discomfort at the site of the bite. This → severity of lacerations lasts for 2-10 days. → distance the virus has to travel from its point of entry to → The acute neurologic phase follows, marked by the central nervous system (higher attack rate and agitation, hallucinations, hydrophobia (fear of water), shorter incubation period in persons bitten on the face aerophobia (fear of air or drafts), hypersalivation, and or head; lowest mortality occurs in those bitten on legs) The G glycoprotein is a major factor in rabies virus ❗ paralysis. Hydrophobia is the most common symptom, happening in 20-50% of cases neuroinvasiveness and pathogenicity. ▪ Anywhere from 15-60% of cases experience ❗→ Encephalitic/ G. CLINICAL MANIFESTATIONS Human rabies presents in two forms: Furious rabies paralysis → The virus spreads to the skin of the head and neck, including the eyes, nose, and salivary glands, the latter → Paralytic/ Dumb rabies of which can transmit the virus to someone else. → After the neurologic phase, which lasts 2-10 days, patients typically become comatose. → As the disease advances, patients may develop encephalitis, coma, and death due to respiratory failure within days of symptom onset if left untreated. 💬 H. CLINICAL MANIFESTATIONS (ADDITIONAL 💬 Clinical Findings NOTES) → acute, fulminant, fatal encephalitis → incubation period in humans is typically 1-3 months ❗ (usually shorter in children than in adults) Clinically, the disease in humans is divided into the same three phases as dog rabies 1. Prodrome (2-10 days): malaise, anorexia, headache, photophobia, nausea and vomiting, sore throat, and fever 2. Acute neurologic phase (2-7 days): nervousness, apprehension, hallucinations, and Figure 7. Rabies clinical manifestations [Youtube] bizarre behavior, lacrimation, pupillary dilatation, and The clinical manifestations of rabies typically progress increased salivation and perspiration, hydrophobia through prodromal, acute neurologic, and paralytic (fear of water because act of swallowing precipitates phases. a painful spasm of the throat muscles) or aerophobia (fear when feeling a breeze). 3. Convulsive seizures or coma and death via cardiorespiratory arrest. I. DIAGNOSIS Involves a combination of clinical presentation, history of exposure to a rabid animal, and laboratory testing. Definitive diagnosis typically requires direct fluorescent antibody (DFA) testing or reverse MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 3 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE transcription-polymerase chain reaction (RT-PCR) on → Other animals should be held for observation for 10 samples obtained from skin biopsies of the nape of the days. If they appear normal after 10 days, decisions ❗️ neck or post-mortem brain tissue. must be made on an individual basis in consultation with → (+) Negri bodies on post-mortem brain tissue, the public health officials. 💬 classic histopathologic feature of rabies. K. TREATMENT → Presence of Negri bodies (eosinophilic cytoplasmic Post-exposure prophylaxis (PEP) is the cornerstone of inclusion filled with viral nucleocapsids in infected nerve rabies treatment following exposure to a potentially rabid cells) is pathognomonic of rabies but its absence does animal. not rule out rabies as a diagnosis. PEP involves thorough wound cleansing with soap and water, followed by administration of rabies vaccine and rabies immune globulin (RIG) as soon as possible after exposure. → Rabies vaccines available: ▪ Purified chick embryo cell vaccine ▪ Purified Vero cell vaccine ▪ Human diploid cell vaccine The rabies vaccine stimulates the immune system to produce antibodies against the virus, while RIG provides ❗ immediate passive immunity. PEP are given on days 0,3,7,14, and 28 intramuscularly Figure 9. Negri bodies on post-mortem brain tissue [Youtube] Pre-exposure prophylaxis are given on day 0,7,21, and 28, and indicated for veterinarians and researchers Serological tests to detect rabies-specific antibodies may Once clinical symptoms develop, treatment is primarily also aid in diagnosis, although they are primarily used for supportive, focusing on symptom management and epidemiological purposes or to confirm past exposure palliative care, as the disease is nearly always fatal once to the virus. symptoms appear. J. DIAGNOSIS (ADDITIONAL NOTES) 💬 L. TREATMENT (ADDITIONAL NOTES) 💬 ❗ Laboratory Diagnosis There is no successful treatment for clinical rabies. NO tests to diagnose rabies infections in humans Preexposure Prophylaxis BEFORE onset of clinical symptoms → Indicated for persons at high risk of contact with rabies → Rabies can be diagnosed from tissue biopsies of virus antibody titers should be monitored periodically euthanized animals by direct fluorescent antibody and that boosters be given when required testing (using anti-rabies monoclonal antibodies) of Postexposure Prophylaxis brain tissue. → The decision to administer rabies antibody or rabies ❗ Rabies Antigens or Nucleic Acids vaccine—or both—depends on several factors: A definitive pathologic diagnosis of rabies: Negri ▪ nature of the biting animal & its vaccination status bodies in the brain or the spinal cord (sharply ▪ availability of the animal for laboratory examination demarcated, more or less spherical, and 2-10 um in ▪ existence of rabies in the area diameter, and they have a distinctive internal structure ▪ manner of attack (provoked or unprovoked) with basophilic granules in an eosinophilic matrix. Negri ▪ severity of the bite and contamination by saliva of the bodies contain rabies virus antigens) animal Serology ▪ advice from local public health officials → Serum antibodies to rabies can be detected by Prevention by Vaccine immunofluorescence or neutralization tests. → Virus must be amplified in muscle near site of → Antibodies develop slowly in infected persons or inoculation until concentration of virus is sufficient to animals during progression of the disease but promptly accomplish infection of CNS after vaccination with cell-derived vaccines. → All vaccines for human use contain only inactivated → Antibodies in cerebrospinal fluid are produced in rabies virus. rabies-infected individuals but not in response to → Types of Rabies Antibody vaccination. 1. Rabies immune globulin, human (HRIG)-HRIG Viral Isolation (v-globulin from plasma of hyperimmunized humans; → Available tissue is inoculated intracerebrally into therefore, offers fewer adverse compared to equine suckling mice; infection in mice results in encephalitis anti-rabies serum) and death 2. Anti-rabies serum, equine- concentrated serum from → CNS (+) for Negri bodies and rabies antigen; isolated horses hyperimmunized with rabies virus virus is identified by fluorescent antibody tests with → Prompt administration of vaccine or specific specific antiserum Virus isolation takes too long to be antibody depresses virus replication to prevent CNS useful in making a decision about whether to give invasion vaccine → The action of passively administered antibody is to Animal Observation neutralize some of the inoculated virus and lower the → All animals considered "rabid or suspected rabid" (any concentration of virus in the body, providing additional signs of encephalitis, rabies, or unusual behavior) time for a vaccine to stimulate active antibody should be sacrificed immediately for laboratory production to prevent entry into the central nervous examination of neural tissues. system. MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 4 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE → Successful postexposure prophylaxis will therefore prevent the development of clinical rabies. 🔺 II. PRIONS Prion Disease is caused by a single protein that makes a Immunity and Prevention mistake and misfolds. This misfolded protein can cause → Only one antigenic type of rabies virus is known. (NO other normal proteins to misfold which damage and VARIANTS) destroy cells → More than 99% of infections in humans and other Factors: mammals that develop symptoms end fatally. → Genetics: 10-15% ▪ Survival after the onset of rabies symptoms is → Eating infected meat extremely rare. ▪ Most well known: Mad Cow Disease ▪ It is therefore essential that individuals at high risk → Sporadic receive preventive immunization, that the nature and risk of any exposure be evaluated, and that 🔺 A. WHERE PRION PROTEINS GO individuals be given postexposure prophylaxis if their exposure is believed to have been dangerous ▪ Because treatment is of no benefit after the onset of clinical disease, it is essential that postexposure treatment be initiated promptly. ▪ Postexposure rabies prophylaxis consists of the immediate and thorough cleansing of all wounds with soap and water, administration of rabies immune globulin, and a vaccination regimen. M. STREET VS FIXED VIRUS Figure 13. Where prion proteins go [Youtube] In the lymph node, there are: → B cells (orange) → T cells (blue) → Dendritic cells (purple) B and T cells live for a very long time while dendritic cells live between weeks to months. Lymph nodes are located throughout your body specifically the base of your neck, armpits, behind knees and a human has about 700 of them If you consume a prion protein (pink heart cells), they will Figure 10. Rabies- street vs fixed virus[Youtube] circulate throughout your body because they are hard to destroy N. RISK CATEGORIZATION AND ANTI-RABIES → When the dendritic cells encounter these misfolded PROPHYLAXIS proteins, it’s going to consume them in a process called phagocytosis or cell eating → As it brings the prions into the cell, the body puts it in a vesicle and that means it now has access to the inside of the dendritic cell which tries to fight it off Dendritic cell or most immune cells try to destroy it with acid and enzymes which typically works → It destroys it through lysosomes. It has a pH similar to the stomach between pH 1-2. → Typically, it breaks proteins down but prions are resistant to this process → The killing is unsuccessful and dendritic cell is still full of Figure 11. Rabies- risk categorization[Youtube] prions Dendritic cell break down the prion proteins through another mechanism called proteasome-ubiquitin pathway → They tag misfolded proteins with ubiquitin. It’s like putting a red flag on them and they are taken to the proteasome which is the scissors within the cell that cuts up misfolded proteins → However, prions are also resistant to this pathway so the misfolded proteins will get free from the vesicles and interact with healthy dendritic prion proteins Affected dendritic cell interacts with nearby healthy prion proteins and causes it to misfold. This is why it can take such a long time for a person to experience the effects Figure 12. Rabies PEP guide[Lecturer’s notes] from prion disease MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 5 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE It could take up to 20 years for a person to realize that SUMMARY ❗ they have prion disease Prions are normal proteins in most mammals → Because prions have to make it all the way to a lymph Most concentrated in the brain and spinal cord node to be consumed by a dendritic cell and it has to Majority of the time when prions become disease travel across a series of lymph nodes depending on related it's due to something sporadic how far it is from the blood-brain barrier → Doctors and researchers don’t always know the case People who have prion disease experience terrible Sometimes, it has to do with eating infected meat symptoms such as dementia and loss of brain cells because the brain and spinal cord are rich in prion because dendritic cells are going to carry the prion protein proteins across the blood brain barrier if you happen to consume it from another animal's brain → Once the dendritic cell crosses the BBB, they are able and spinal cord you could potentially get the mutated to access neurons and damage them leading to prion which then over time could traffic from your dementia intestines to your lymph node replicate in your lymph nodes dendritic cells → Over the course of years gain access to your BBB and then destroy your neurons which results in the dementia symptoms 15% of the time - it is genetic, some people have altered prion codes and when they’re translated to a protein in the brain, they start to misfold on their own 85% of the time - it is sporadic, not understood how it ❗ happened but subset of those are due to infection Ways to get prion disease: → Family history → Eating infected meat → Sporadic Figure 14. Where prion proteins go [Youtube] C. PRIONS (ADDITIONAL NOTES) 💬 Transmissible Spongiform Encephalopathies Inside the brain, there is a dendritic cell and it’s going to → Prions ❗ interact with a neuron Prion proteins is highest concentrated in the brain ▪ Proteinaceous material devoid of detectable amounts of nucleic acid ❗ and spinal cord Lymph nodes is the third most concentrated Prion infected dendritic cell took months to years for it to ▪ Acquisition of misfolded prion proteins that can cause misfolding and aggregation of normal cellular prion protein expressed in brain tissue cross the BBB ▪ Guanidine thiocyanate is highly effective in Once it reaches the brain, the neurons will pick up the decontaminating medical supplies and instruments misfolded proteins and then all of the prion proteins inside → Hallmarks the neuron will become damaged ▪ Prions may be recoverable from other organs, but the Normal healthy prion proteins are very important to diseases are confined to the nervous system. neurons ▪ The basic features are neurodegeneration and → Used in synapses where neurons communicate to one spongiform changes another ▪ Long incubation periods (months to decades) → Also important for cell signaling, support, scaffolding precede the onset of clinical illness and are followed Infected misfolded dendritic cell infecting the neurons by chronic progressive disease (weeks to years) cause inflammation ▪ Always fatal, with no known cases of remission or → Studies in rodents indicate that immune cells of the recovery brain microglia play a role ▪ Host shows no inflammatory response and no → Microglia with long branches - resting state immune response (the agents do not appear to be ▪ Typically just surveying the environment and antigenic); no production of interferon is elicited; and supporting the neuron’s health there is no effect on host B-cell or T-cell function → Blobby, amoeboid microglia - activated ▪ Immunosuppression of the host has no effect on ▪ Occurs when misfolded proteins are around or when pathogenesis neurons are damaged Activated microglia produce cytokines which are 🔺 C. PRION DISEASES neurotoxic → TNF-α → IL-1 beta → IL-6 These neurotoxic cytokines can directly and indirectly kill neurons There’s some debate as to whether the prion proteins themselves can be neurotoxic or whether or not it requires participation from the immune cells as microglia Figure 15. Common prion diseases [Youtube] MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 6 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE Scrapie - causes sponge-like holes in sheep brain Instead, it results from mutations in the PrP gene that Mad cow disease make PrPᶜ more prone to spontaneously adapt the PrP​​Sc → Formally known as bovine spongiform encephalopathy conformation (BSE) Once in a PrP​Sc ​ conformation, it causes more PrPᶜ to → Variant of scrapie adapt the PrP​​Sc conformation regardless of whether it → Infected tissue is identified by the holes left by neuronal carries the mutation or not degeneration When wild-type mice are infected by PrP​​Sc, they die Creutzfeldt-Jakob disease/ CJD - rare inherited disease invariantly within a certain period of time due to massive in humans neural degeneration Kuru - spread through ritual cannibalism However, mutant PrP knock-out mice are resistant to PrP ROLE OF PRIONS infection It has subsequently been discovered that protein induced Induced conformational change in proteins called prions is protein conformational change may also contribute to other the root cause of these fatal diseases types of neurodegenerative diseases such as Parkinson's and Huntington's 🔺 III. CREUTZFELDT-JAKOB DISEASE Rare but fatal degenerative brain disorder Different types of CJD: → Sporadic CJD: ▪ Most common type ▪ Cause: unclear, hence “sporadic” − Normal brain protein, a “prion” misfolds to create an abnormal protein → Variant CJD: Figure 16. Electron micrograph from a sheep with scrapie ▪ Most people have heard of [Youtube] ▪ Cause: consuming infective material such as meat from a cow that had bovine spongiform In the electron micrograph, there is an aggregation of encephalopathy or mad cow disease prions that have formed irregular rod structures thought to → Familial CJD: cause disease ▪ Very rare ▪ Cause: one of the genes encoding the normal prion protein carries a mutation that causes abnormal prions to form in the brain during adulthood → Iatrogenic CJD: ▪ Cause: infection is accidentally spread from someone with CJD through medical or surgical treatment − For example: through a contaminated corneal transplant or through a blood transfusion ▪ This is very rare and nowadays steps are taken to minimize the risk of contamination during these Figure 17. PrPᶜ adapting to PrP​​Sc conformation [Youtube] procedures What is a prion? PrPᶜ - cell surface protein produced by most cell types → Prions are a normal structural component of the → Has three alpha helices - A, B and C nervous system. → Two short β strands → However it can become misfolded into an abnormal or PrP​Sc ​ - isoform of PrPᶜ that was identified as the infectious diseased prion protein. agent in scrapie ▪ misfolded prion proteins can catalyze the conversion → Has only two alpha helices - B and C of normal prion proteins into abnormal ones in a → A β strand chain reaction. ❗ ▪ More susceptible to aggregation → Abnormal prion proteins accumulate in the brain and Presence of PrP​Sc ​ can cause PrPᶜ to adapt the can cause irreversible damage. PrP​Sc ​ conformation ▪ Macroscopically: brain atrophy or wasting. PrP​Sc ​ proteins form intersecting rod-like aggregates ▪ Microscopically: vacuolation in the gray matter. through interactions of their beta-pleated sheets − Give the brain a spongy appearance histologically, The accumulation of these aggregates causes cell death thus “spongiform encephalopathy”. and extensive tissue damage → No treatment for CJD → Damage can propagate from cell to cell and even Pathology through digestive systems when the disease material is → Neuronal loss -> brain atrophy eaten by healthy animals → Astrocytic proliferation and cytoplasmic vacuoles in → It also catalyzes the conversion of PrPᶜ to PrP​Sc neurons and astrocytes -> brain w/ spongy appearance Presentation of CJD is variable but symptoms are often CREUTZFELDT-JAKOB DISEASE rapidly progressive Unlike scrapie or mad cow disease, it does not require → ⅓ experience fatigue sleep problems and reduced infectious protein agents appetite MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 7 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE → ⅓ have general neurological problems including: ▪ Lead to splenic rupture ▪ memory loss or dementia behavioral changes and → Commonly seen in teenagers confusion → A way that examiners test EBV would be that if a patient → ⅓ have more focal neurological signs including: with a sore throat develops rash after being given ▪ cerebellar ataxia aphasia visual disturbances or amoxicillin. motor weakness → Diagnosed by: Mono-spot test → In a patient presenting with these symptoms it would be ▪ Negative important to examine the cerebrospinal fluid to rule out − May be due to when the test was taken. If too infection as the cause early: false negative Must also rule out toxicity with drugs or alcohol − Not due to EBV, but CMV (cytomegalovirus) Definitive diagnosis for CJD is with a brain biopsy however instead this is usually done post-mortem 🔺 IV. TOP 7 VIRUSES THAT CAN CAUSE CANCER A. VIRUSES HHV-8/Kaposi Sarcoma → DNA Virus → Associated with: HIV/AIDS ▪ Most common AIDS defining malignancy → Purple macules in the face, arms, and lower extremities → Commonly seen in Africa → Can occur in immunosuppressed patients sporadically. → Treatment: Highlight Active Anti-Retroviral Therapy Figure 19. EBV [Youtube] (HAART) Hepa B and C → DNA Viruses → Lead to Hepatocellular Carcinoma → 2 risk factors ▪ Cirrhosis ▪ Infection w/ Hepatitis Virus → Prevention: Administer Hepa B Vaccine → ONCOGENIC VIRUSES HANDOUT: ▪ HEPATITIS B VIRUS (HBV) Figure 18. Kaposi Sarcoma [Youtube] − causes chronic hepatitis & is a risk factor in the development of hepatocellular CA HPV/Human Papillomavirus − necrosis, inflammation, regeneration, cirrhosis → DNA Virus − X protein (HBV transactivator protein) + aflatoxin → Associated with: (dietary carcinogen cofactor) play roles in ▪ Anal cancer hepatocellular CA transformation ▪ Cervical cancer − Hepatitis B vaccine for prevention of primary ▪ Penile cancer infection & possible prevention of hepatocellular ▪ Head and Neck cancers CA → Strains: ▪ HEPATITIS C VIRUS (HCV) ▪ 1 & 4: Plantar Warts − Causes chronic hepatitis, cirrhosis, and is a ▪ 6 & 11: Genital Warts causative factor in hepatocellular CA ▪ 16, 18, 31, 33, 45: Cervical Cancer HTLV-1/Human T-cell Lymphotropic Virus Type 1 ▪ HPV Vaccines mainly for prevention of genital warts → Lead to T-cell lymphoma/Leukemia and cervical cancer → Associated with: → Cervical cancer screening ▪ Cutaneous lesions ▪ Initiated in sexually active women at age 21-65 ▪ Lytic bone lesions − 21-30 y/o: Cytology/Pap smear every 3 yrs ▪ Pulmonary infiltrates − 30-65 y/o: Cytology + HPV testing every 5 yrs → Can experience hypercalcemia → Prevention: HPV Vaccine and Pap smear HIV/Human Immunodeficiency Virus − Vaccine: Men and Women. Early as 9 y/o → RNA Virus Epstein-Barr Virus → Likely to develop cancers due to decreased immune → DNA Virus response → Acute infection lead to infectious mononucleosis AKA → Can cause most of the aforementioned cancers “mono” or kissing disease → Most common AIDS defining malignancy → Associated with: ▪ Kaposi Sarcoma ▪ Hodgkin’s Lymphoma ▪ Cervical cancer ▪ Burkitt’s Lymphoma ▪ CNS lymphoma ▪ Post-transplant Lymphoma ▪ Nasopharyngeal Carcinoma B. BACTERIA → Have history of sore throats and posterior H. Pylori lymphadenopathy → Gram-negative → Most serious complication: Splenomegaly → Spiral-shaped MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 8 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE → Associated with: 2. D. Patient is considered immunocompromised due to ▪ Peptic Ulcer Disease HIV → Chronic Illness: C. ONCOGENIC VIRUSES ADDITIONAL NOTES ▪ Maltoma ASSOCIATION OF VIRUSES WITH HUMAN CANCERS Figure 20. H. Pylori [Youtube] Bartonella Henselae → Gram-negative → Rod-shaped → Replicates in RBC (refer to Figure 15, red arrows) → Develop cat scratch disease ▪ Tender lymphadenopathy 2 weeks after exposure ▪ Presence of wheal or papule at site of trauma ▪ Experience fatigue, fever, myalgia → Bacillary angiomatosis: multiple cluster of papules, plaques on skin and mucosa → Associated with: ▪ Bone pain ▪ Weight loss ▪ Fever ▪ Night sweats Figure 22. Fundamental differences exist between the oncogenes of DNA and RNA tumor viruses. [Handout] DNA tumor viruses encode viral oncoproteins that are important for viral replication and affect cellular growth control pathways. Figure 21. H. Pylori [Youtube] RNA tumor viruses carry an oncogene of cellular origin (direct transforming) or weakly oncogenic (ex. HIV, HTLV CONCEPT CHECKPOINT & HCV) which do not contain an oncogene and induce 1. What virus most likely caused this patient’s leukemias after long incubation periods by indirect condition? mechanisms (slowly transforming). a. HTLV-1 b. HPV MOLECULAR MECHANISMS OF CARCINOGENESIS c. HHV-8 Cellular Oncogenes d. Influenza → genes that are involved in cancer causation → Normal cells have proto-oncogenes (normal versions of these transforming genes) ▪ responsible for regulating cell proliferation, division, and differentiation and for maintaining the integrity of the genome. → Incorrect expression of proto-oncogenes (genetic damage) interrupts regulation, resulting in 2. 23 y/o woman who is known to have HIV came to overexpression & uncontrolled growth of cells (cancer). do her Pap smear. How often should she repeat her → Examples Pap smear? ▪ tyrosine-specific protein kinases (eg, src) a. every 3 years ▪ growth factors (sis is similar to human b. every 2 years platelet-derived growth factor, a potent mitogen for c. every 5 years cells of connective tissue origin) d. per annum ▪ mutated growth factor receptors (erb-B is a truncated epidermal growth factor receptor) ANS: ▪ GTP-binding proteins (Ha-ras) 1. C. Kaposi Sarcoma ▪ nuclear transcription factors (myc, jun). MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 9 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE Tumor Suppressor Genes Initial infection of oncogenic viruses incites immune → negative regulators of cell growth response. Successful immune defense results in virus → inactivation or functional loss of both alleles of such a control and elimination. gene is required for tumor formation In some cases, oncogenic viruses persist due to evasion → Example strategies. ▪ retinoblastoma (Rb) gene Persistent oncogenic viruses may proceed to viral ▪ p53 gene carcinogenesis, especially during immunosuppressive conditions. CELL SUSCEPTIBILITY TO VIRAL INFECTIONS AND TRANSFORMATION Figure 26. Cell Susceptibility to Viral Infections and Transformation [Handout] Oncogenic viruses exhibit marked tissue specificity due to Figure 23. Examples of DNA Virus Oncoproteins and Cellular variable presence of surface receptors or the virus Protein Interactions [Handout] Not all cells from the natural host species are susceptible to viral replication or transformation or both. POLYOMAVIRUSES MULTI-STEP MECHANISMS OF ACTION BY HUMAN CANCER VIRUSES Figure 24. Multi-step Mechanism of Action by Human Cancer Virus [Handout] Figure 27. Important Properties of Polyomaviruses [Handout] HOST IMMUNE RESPONSES Human polyomaviruses BK and JC are widely distributed in human populations; infection usually occurs during early childhood & immunocompromised patients BK virus: causes hemorrhagic cystitis, polyomavirus-associated nephropathy JC virus: causes progressive multifocal leukoencephalopathy Merkel cell polyomavirus causes Merkel cell carcinomas Figure 25. Host Immune Response [Handout] MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 10 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE HERPESVIRUSES → These viruses are typically contracted through sharing of needles, engaging in unprotected sex, or receiving transfusion involving contaminated blood → HCV infections can often be successfully cleared with several months of treatment → While medication does not provide a cure for HBV, it can significantly reduce risk of liver damage and the development of liver cancer → A vaccine is available for prevention of HBV, but there is currently no vaccine for HCV. Those at a heightened risk of HBV transmission, such as individuals with HIV, individuals who use illicit injection, or healthcare workers, should consider getting vaccinated Kaposi Sarcoma-Associated Herpesvirus (KSHV) → KSHV, a herpes virus, has the potential to induce Kaposi sarcoma, a cancer affecting blood vessels, as well as 2 forms of lymphoma → risk of developing cancer due to KSHV is heightened in immunocompromised individuals, resulting from factors such as organ transplantation, chemotherapy, or AIDS. Figure 28. Important Properties of Herpesviruses [Handout] → Transmission: sexual contact, blood, saliva Merkel Cell Polyomavirus (MCV) EBV: causes acute infectious mononucleosis; Burkitt → Prevalent virus that can infect the skin lymphoma → typically remains asymptomatic and does not result in Kaposi sarcoma–associated herpesvirus AKA human cancer herpesvirus 8 (KSHV/HHV8): causes Kaposi sarcoma, → MCV can trigger a rare form of skin cancer known as primary effusion lymphoma, and multicentric Castleman Merkel cell carcinoma disease, a lymphoproliferative disorder. Human Papillomavirus (HPV) → comprises a collection of over 200 viruses, with approximately a dozen known to have the potential to HOW TO PROVE THAT A VIRUS CAUSES HUMAN cause virus CANCER → transmission: vaginal or anal sexual contact The following criteria can be difficult to establish if other → In many cases, HPV infections spontaneously clear up environmental or genetic factors cause some cases of and do not result in any health issues. However, some the same type of cancer. Only if the continued individuals may remain infected expression of a viral function is necessary for → persistent infection with cancer-causing HPV strains can maintenance of transformation will viral genes necessarily lead to cancers including those of cervix, vulva, vagina, persist in every tumor cell. penis, anus, tonsils, or tongue → If a virus is the only etiologic agent of a specific cancer, → HPV vaccines are available. Recommended for young the geographic distribution of viral infection should women up to 26 years old and young men up to 21 coincide with that of the tumor. years old → The presence of viral markers should be higher in Human T-cell Lymphotropic Virus Type 1 (HTLV-1) cases than in controls. → Targets T cells, a subset of WBC, and has the potential → The viral infection should precede the tumor. to induce leukemia and lymphoma The most definitive proof of a causal relationship is → transmission: mother to child, breastfeeding, sharing dec/leukemia increased tumor incidence by prevention of needles w/ infected individuals, organ transplantation, viral infection. Intervention methods should be effective in unprotected sex reducing the occurrence of the cancer even if the virus is → No known cure or specific treatment for HTLV-1, 🔺 only one of several cofactors. making it a lifelong condition. However, regular medical V. FROM VIRUS TO CANCER checkups can help reduce the risk of developing cancer. The process of viral replication can lead to alterations in Epstein-Barr Virus (EBV) the host cell’s genes, potentially contributing to the → EBV can lead to mononucleosis and more severe development of cancer. illnesses, including viral meningitis and pneumonia Oncoviruses are a category of viruses capable of inducing → Linked to Burkitt’s lymphoma, nasopharyngeal cancer carcinoma, Hodgkin’s and non-Hodgkin’s lymphoma, Approximately 20% of all human cancer cases are T-cell lymphomas, post-transplant lymphoproliferative attributed to viral infections disorder, and leiomyosarcoma numerous viruses can induce tumors in animals, there are → No current vaccine to prevent EBV currently only 7 viruses known to be associated with Mechanism of viral oncogenesis human cancers and classified as oncogenic viruses → The molecular processes involved in viral oncogenesis Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are intricate and may encompass: → HBV and HCV have the potential to initiate liver → Initiation of chronic inflammation infections, which in certain cases may progress to liver → disruption of host’s genetic and epigenetic stability and cancer balance → interference with the cellular DNA repair mechanism, resulting in instability of the genome. MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 11 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE → dysregulation of cell cycle → ability of oncogenic DNA viruses to integrate their 🔺 A. HUMAN PAPILLOMA VIRUS Group of non-enveloped DNA viruses genetic material into the host cell’s chromosomes, Specifically infect human epithelial cells causing genetic abnormalities. categorized by the epithelial cells they prefer to infect → activation of cellular signaling pathways by viral cutaneous epithelial cells of skin: face, hands, feet “oncoproteins”, which can modify the expression of mucous membranes: respiratory tract including pharynx, cellular genes and microRNAs at the transcriptional or nasal, and oral cavities post-transcriptional levels. These oncoproteins can also some type can cause benign tumors called PAPILLOMAS destabilize or deactivate proteins responsible for or WARTS controlling cell polarity, signal transduction, immune some can lead to CARCINOMAS (cancer of the epithelial responses, and apoptosis. cells) → genetic and epigenetic changes induced by infection Epithelial cells: line the outer surfaces of organs & blood and replication of oncogenic viruses may lead to the vessels, separate the interior of the body from external emergence and proliferation of cancer stem cells. These world, serve as protective barrier cells play a pivotal role in the initiation, advancement, As the basal cells divide and mature, they move toward the metastasis, recurrence, and resistance to chemotherapy outermost layer, flattening out and becoming more in cancers. A. SLOW VIRUSES (ADDITIONAL NOTES) 💬 squamous shaped in appearance. Once they reach the top layer, these mature, flat cells are exfoliated, or shed, from Subacute Sclerosing Panencephalitis the epithelium. → Caused by measles virus Now, typically basal cells are well protected under all those → Fatal, slowly progressive demyelination in the CNS layers. But if there are abrasions or cuts in the epithelium, ▪ Large numbers of viral nucleocapsid structures are HPV can gain access to and infect the basal cells. Once produced in neurons and glial cells that happens, HPV can replicate with or without being ▪ Restricted expression of viral genes that encode incorporated into the basal cell’s DNA through the activities envelope proteins → virus in persistently infected of two particular viral genes called E6 and E7. The neural cells lack proteins needed to produce proteins of these genes cause dysregulation of infectious particles tightly-scheduled replication of the epithelial cells by ▪ Hosts have high titers of anti-measles antibody but altering the p53 and retinoblastoma protein (pRB) tumor antibody to M protein is lacking suppressor pathways that typically prevent unregulated ▪ Reduced efficiency of measles virus transcription in growth of the epithelial cells. differentiated brain cells → infection → SSPE In this way, HPV causes uncontrolled replication of the Progressive Multifocal Leukoencephalopathy (PMLE) epithelial cells, forming warts, and disrupts the normal → Caused by JC virus (polyomaviridae) structure of the epithelium, forming lesions. → CNS complication (demyelination) in immunosuppressed individuals (AIDS) when JC virus reactivates VI. HUMAN PAPILLOMAVIRUS 💬 Figure 30. Koilocyte [Youtube] In some types of HPV infections, a squamous epithelial cell can become a koilocyte, or a cell with an irregular shape, enlarged and dark staining nucleus, and a clear area around the nucleus that’s called a perinuclear halo. These cells are typical of precancerous lesions that can transform into carcinomas when the abnormal epithelial cells break through the basement membrane of the epithelium and invade other tissues. The cause of an HPV infection is contact with infected epithelial cells. Some activities can increase the risk of exposure, like having multiple or new infected sexual Figure 29. Papillomavirus [Handout notes] partners, or delivering a baby through an infected birth Peak incidence of HPV infections: adolescents and young canal. Infections are more likely if a person is already adults younger than 25 years. immunocompromised. Transformation to carcinomas is Men are carriers, vectors of HPV; most penile HPV dependent on HPV type and aided by other cofactors like infections in men are subclinical and do not result in tobacco use, immunosuppression, and radiation. HPV-associated disease. High-risk patients: Immunocompromised; men who have sex with men; (+) HIV/AIDS Diagnosis: Papanicolaou (Pap) smear for cervical CA; DNA hybridization or PCR methods. HPV Vaccines MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 12 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE 18. Condom use should also be considered a measure of prevention. Summary: Human papillomavirus is a DNA virus spread through contact that infects human epithelial cells of the skin and mucous membranes. Symptoms can range from warts, to precancerous lesions and carcinomas. → Definitive diagnosis can be made molecularly and Figure 31. Different type of warts caused by HPV[Youtube] treatment can range from allowing the immune system Now, many HPV infections are asymptomatic, but when to clear the infection, to mechanical or chemical removal symptoms are present, they can vary by HPV type. So, of infected cells. symptoms of nongenital cutaneous infections can involve some kind of benign wart. VII. RETROVIRUS REVERSE TRANSCRIPTION → Common skin warts of the hands or nails are typically painless, dome-shaped projections that give the skin a rough appearance. Plantar warts on the soles of the feet can be painful, and scaly → Flat warts of the face and extremities, particularly in the pediatric population, are often painless, small, smooth, and flat-topped but numerous. → Filiform warts of the face, particularly the eyelids and lips, have long projections that appear thread- or finger-like. → In rare cases, where there is an underlying genetic disorder called epidermodysplasia verruciformis, a chronic cutaneous infection can start out as flat warts and transform into skin cancer. Infections of mucous membranes like the upper respiratory tract, can cause respiratory papillomatosis and can lead to voice changes and high-pitched breath sounds, particularly if the larynx is infected. Anal and genital infections (like the female vulva, cervix Figure 32. Important Properties of Retroviruses[Handout notes] and vagina; and male penis and scrotum), can involve Latent periods; normally expressed at low, carefully numerous warts called condylomata acuminata. They regulated levels becoming activated and expressed tend to be skin-colored and can range in size, but have a constitutively cauliflower-like look to their surface. Though they are Human T-Lymphotropic Viruses (HTLV) 1 & 2 cause typically painless, they can cause itching, burning, local adult T-cell leukemia-lymphomas (ATL) pain, or bleeding. o Transmission: breastfeeding, blood transfusion, Now, HPV types 6 and 11 are responsible for the majority sharing blood-contaminated needles (drug of laryngeal papillomatosis and genital warts and are abusers) and sexual intercourse. considered low-risk HPVs because they don’t tend to Human Immunodeficiency Viruses causes acquired progress beyond warts. high-risk HPV types like types 16 immune deficiency syndrome (AIDS) and 18 have a high risk of transforming into cancers of the o Associated with cervical cancer, Kaposi cervix, vagina, vulva, penis, anus, or upper respiratory sarcoma, lymphomas, head and neck cancer, tract over one or two decades. liver cancer, and oral cancer Warts are used to diagnose HPV, particularly in cutaneous infections. Infections of mucous membranes may require additional interventions to visualize epithelial cells. An endoscopy, a tube with a camera at the end, may be needed if an infection of the upper respiratory tract is suspected; and regular pap or acetic acid tests of the cervix after 21 years old are recommended even if symptoms are sub-clinical. A definitive diagnosis of HPV can not be made without molecular testing of biopsied cells for viral DNA or RNA. So treatments often center around removal of warts and precancerous lesions with salicylic acid products, liquid nitrogen cryotherapy, or laser or surgical removal. In cases of frequent re-occurrences, immune modifiers Figure 33. Different type of warts caused by HPV[Youtube] may be used to help boost the immune system to remove the infection on its own. Most HPV infections can resolve So this is HIV, it's a typical retrovirus meaning that it has an on their own over time, particularly with low-risk types and outer envelope and in the center it has two copies of RNA in younger people. But really, prophylaxis against infection, as well as an enzyme(blue) that's reverse transcriptase is the best course. But limiting contact with potentially which will ultimately turn that RNA into DNA. infected persons; or receiving the HPV vaccine before first The virus itself with this outer envelope protein actually exposure to an infection source can also be protective directly infects T helper cells. The way that it does this is against several strains, including high-risk types 16 and that as it comes up to the cell surface it uses receptors that MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 13 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE are on T helper cells and exclusive to T helper cells which as a some of the enzymes are part of that complex. This are CD4 molecules which really defines T helper cells. it's then buds off at the cell surface at this point but it's still not a surface receptor that binds to the envelope protein it that a mature very on because the polyprotein chain needs to causes a conformational change and allows a second still be digested into its component parts that's done by an receptor to grab hold of the envelope this is the key enzyme called protease. making co-receptor it's also called CCR Protease breaks up those polyprotein chains and ultimately allows for them to coalesce and form the mature structures that make up the final virion and now you have a mature infectious virion that can go on now to infect other cells. Once that happens now the cell can produce tons of viruses and this is really what then keeps the whole process going. 🔺 VIII. HIV & AIDS HIV is the Human Immunodeficiency Virus. If you have HIV, you have an infection that damages your immune system over time, and causes AIDS. AIDS stands for Acquired Immunodeficiency Syndrome. It is the final stage of an HIV infection, when your immune system is damaged and too weak to fight off Figure 34. Envelope Protein Piercing[Youtube] ordinary infections. When foreign invaders, such as bacteria and viruses, get What happens now is that the stock of the envelope into your body, they can cause infections. These events protein pierces through the from the virus into the into the activate your body's defenses. The white blood cells of host cell and starts to draw the two cell membrane the cell your immune system are part of your body's defenses. membrane in the viral membrane together and what One type of white blood cell, called helper T ultimately happens is fusion of those two membranes and lymphocytes, or helper T cells, strengthen your immune the viral genetic material is injected essentially into the cell system's response to infection in two ways. and the envelope protein is left at the cell surface First, helper T cells release chemicals that attract other The virus has a matrix and a capsid protein that essentially white blood cells to the site of the infection. These are digested when it enters into the cell that releases the additional white blood cells attack the invading bacteria or viral enzymes in the viral RNA virus, as well as other infected cells. Reverse transcriptase which takes the viral RNA and Second, helper T cells release chemicals that cause other using host nucleotides converts that viral RNA into a single white blood cells to multiply. These new white blood cells strand of DNA while it does that it makes some random create markers, called antibodies, which can identify the errors which is characteristic of reverse transcriptase. It same foreign invader throughout your body. Antibodies has very poor proofreading activity that single-stranded attach to the bacteria or virus, marking them as targets for DNA now is again reverse transcribed into a double your immune system to destroy them. stranded DNA at that point another enzyme that has come If you have HIV, it travels through your blood and other in with the virus in the beginning called integrase body fluids to infect and kill certain white blood cells. The essentially grabs hold of that double-stranded DNA and virus enters helper T cells, which are the primary target. carries it through a nuclear pore into the nucleus of the Once inside, the virus makes many copies of itself. As cell. Within the nucleus of the cell it finds the host these virus particles are made, they leave the damaged chromosome and it basically the integrase enzyme makes helper T cells to infect other cells. a nick in the host DNA and allows for HIV to insert itself The T cell loses its ability to protect the body from the into the host chromosome and that right there is what ongoing infections and dies. In this way, HIV spreads and establishes lifelong infection. kills more of your helper T cells, weakening your immune RNA polymerase comes along and makes messenger system. RNA. Those messenger RNAs encode for different viral As a result, other types of infections are able to take proteins they end up associating with ribosomes on at the advantage of your body’s inability to defend itself. These surface of the rough endoplasmic reticulum and a piece of infections are called opportunistic infections. mRNA that's making envelope protein which is directly If you have HIV infections, and one or more produced into the endoplasmic reticulum and it's shuttled opportunistic infections, you have AIDS. them through the endoplasmic reticulum and taken to the Some of the common AIDS-related opportunistic infections cell surface where at the cell surface it becomes → Meningitis - inflammation of the tissues covering the embedded in the cellular membrane. At this point brain and spinal cord coalescing with other envelope proteins that have been → Encephalitis - inflammation of the brain produced you have this cluster of envelope proteins now → Respiratory illnesses, such as Pneumonia and on the surface of this infected cell Tuberculosis At the same time there are other messenger RNAs that are → Chronic diarrhea caused by infectious parasites being produced that allow for translation of other viral → Cancer, such as Kaposi’s sarcoma and non-Hodgkin proteins. So here are additional viral proteins being made lymphoma which are going to be used to make up the key HIV passes from person to person through infected body components that the virus ultimately is going to need these fluids. HIV can enter your body through the following: are transported again to the cell surface to the area where → Unprotected sex (semen, vagina, fluids, blood) these envelope proteins are and a strand of RNA as well → Sharing drug injection needles (blood) MICROBIOLOGY Oncogenic, Slow Viruses, HIV PAGE 14 of 20 MICROBIOLOGY | LE 2 Oncogenic, Slow Viruses, HIV | Eric Constantine G. Valera, MD, MHSE → Childbirth (blood, amniotic fluid, vaginal fluid) → Breastfeeding (breast milk) → Contaminated blood and blood products Although there is no cure for HIV, drugs called antiretroviral medications can reduce the amount of HIV in your body. One class of antiretroviral medication called entry or fusion inhibitors, disrupts the HIV infection process by preventing the virus from attaching to your cells. Other classes of antiretroviral medications include → Reverse transcriptase inhibitors → Protease inhibitors → Integrase inhibitors These drugs prevent the creation, assembly, and spread of new viruses. Your doctor may prescribe a combination of these drug classes, known as Highly Active Figure 35. HIV & AIDS [Youtube] Antiretroviral Therapy (HAART). Antiretroviral medication doesn’t completely remove HIV We now know that human immunodeficiency virus is a from your body, but slows it down enough to enable your retrovirus that attacks the body’s immune system, and can immune system to fight infections. lead to AIDS if not treated. Regular blood tests will let your doctor know how effective B. RETROVIRUS your antiretroviral medication is in controlling HIV. If the number of helper T cells is high enough in your blood sample, your medication is working. Treatment for the opportunistic of AIDS are medications specific for each type of infection. For example, Antibiotics for Pneumonia or Tuberculosis. A. HOW TO AVOID HIV INFECTION Know your HIV status and your partner’s status by getting tested regularly Avoid vaginal and anal sex Figure 36. Retrovirus [Youtube] → The most effective way to prevent HIV infection Enveloped Limit sex to one uninfected partner Positive-strand RNA viruses → You will be less likely to contract HIV Have unusual morphology and replication strategies Use latex condoms for protection → Have a capsid containing two copies of a Avoid using injectable illegal drugs or shared needles positive-strand RNA genome → The needles may have the virus on them Avoid intoxication from drugs or alcohol → You will be more likely to engage in unsafe sexual behavior 🔺 IX. HUMAN IMMUNODEFICIENCY A. HISTORY VIRUS (HIV) Human immunodeficiency virus began circulating and infecting humans long before we knew what it was and where it came from, as with most diseases in human history. HIV