Lecture 7: Introduction to Medical Virology (DNA Viruses) - Summer 2024 - Ahram Canadian University PDF

Parasitology & Virology (PM222, PMC222) Summer 2024 Lecture 7 Introduction to Medical Virology DNA viruses Course Instructor: Maha Eid Omran Associate Professor of Microbiology & Immunology 30/7/ 2024...

Parasitology & Virology (PM222, PMC222) Summer 2024 Lecture 7 Introduction to Medical Virology DNA viruses Course Instructor: Maha Eid Omran Associate Professor of Microbiology & Immunology 30/7/ 2024 1 To classify the most medically important viruses. 2 Lec. (7) D./ Maha E. Omran Interactive teaching methods activities: 1. Open Discussion with students. 2. Class activity. 2. Formative questions. 3  44 Lec. (7) D./ Maha E. Omran Lec. (7) D./ Maha E. Omran … Is it different from bacteria? 1. Size 4. Replication 2. Structure + 5. Antivirals function 3. Culture 6. Lab diagnosis 7. Effect of different agents 5 Lec. (7) D./ Maha E. Omran 1. Virus size 6 Lec. (7) D./ Maha E. Omran Want big impact? Use big image. 7  Viruses are smaller than bacteria, while prions are the smallest infectious agent known. The largest smallpox virus is more than 5 times smaller than E. coli and 50 times smaller than a human red blood cell. Lec. (7) D./ Maha E. Omran 8 2. Structure ▸ Virus structure is unique and totally different from bacteria. ▸ Simply virus has mainly two structures: nucleic acid & protein coat. Not all viruses are enveloped. Lec. (7) D./ Maha E. Omran 9 - All DNA human viruses are ds EXCEPT ?? - All RNA human viruses are ss EXCEPT ?? - +ve RNA or –ve RNA Function site of the genetic material which carries Icosahedral Helical the information of Loss of envelope leads to virulence, replication, loss of infectivity antigenicity. Lec. (7) D./ Maha E. Omran 10 Type of nucleic acid: Viruses contain only one type of nucleic acid as their genetic material, either DNA or RNA (never both). The nucleic acid can be single- stranded (ss) or double stranded (ds). Lec. (7) D./ Maha E. Omran 11 Capsid “protein coat”: The nucleic acid is surrounded by a protein coat called a capsid made up of capsomers. Nucleic acid together with the protein coat is known as nucleocapsid. Some viruses are enveloped inside a lipid envelope. Lec. (7) D./ Maha E. Omran 12 Lec. (7) D./ Maha E. Omran 13 13 3. Culture ▸ As viruses are acellular structures they can’t be cultivated as bacteria at ordinary synthetic media. ▸ They can be cultivated only on live cells such as:  Cell lines (tissue culture)  Chick embryo  Lab. animals Lec. (7) D./ Maha E. Omran 14  Viruses are acellular particles, that are not considered alive by most microbiologists. They are considered obligate intracellular parasites …WHY??? as they depend on the infected cells to produce the required components and to replicate because: 1- they have no ribosomes nor t-RNA for protein synthesis. 2- they cannot produce energy as they are metabolically inactive. 15 Lec. (7) D./ Maha E. Omran 15 4. Replication ▸ Viruses do not replicate as bacteria by binary fission but they can reproduce by special replication cycle. Don’t forget to Watch the video Lec. (7) D./ Maha E. Omran 16 Replication cycle steps 1. Attachment (specific process) 2. Entry or penetration. 3. Uncoating (naked nucleic acid). 4. Protein synthesis & genome replication. 5. Assembly 6. Release (lysis of the cell or by budding) Lec. (7) D./ Maha E. Omran 17 Replication cycle steps Lec. (7) D./ Maha E. Omran 1818 Replication of the virus nucleic acid:  DNA viruses: with the exception of poxviruses, all replicate in the nucleus.  RNA viruses: with the exception of orthomyxoviruses and retroviruses, all replicate in the cytoplasm of the host cell. Lec. (7) D./ Maha E. Omran 19 5. Antiviral drugs Lec. (7) D./ Maha E. Omran 20  Antiviral drugs are few.. Why? G.R. Viruses are the cause of many diseases in humans ranging from AIDS and cancer to the common cold. Microbiologists have developed vaccines for many viral diseases but have not been as successful in discovery of treatments for the diseases. It is the opposite in bacteriology. WHY…??? Try to think in reasons. Lec. (7) D./ Maha E. Omran 21  Antiviral drugs are few in numbers in comparison to no. of antibiotics.. Why? G.R. Try to think in reasons. Lec. (8) D./ Maha E. Omran 22 Replication Antiviral drugs Step targets point in the replication cycle Nucleic a` Ribavirin Zidovudine HIV RNA Acyclovir synthesis RSV & Lamivudine HIV & polymerase Herpes v. HCV HBV inhibitor HCV Amantadine, Rimantadine Ledipasvir + Uncoating Sofosbuvir Influenza A “Harvoni” Oseltamivir “Tamiflu”, zanamivir “Relenza” Release of v. Influenza A Protein INTERFERON synthesis by viral mRNA HBV Lec. (7) D./ Maha E. Omran 23 6. Laboratory diagnosis Lec. (7) D./ Maha E. Omran 24  Identification in cell culture.  Microscopic identification. electron microscope, inclusion bodies by light microscope, fluorescent microscope (fluorescent Ab staining to the v. infected cells).  Serological tests.  Detection of nucleic a`(PCR). Lec. (7) D./ Maha E. Omran 25  1- Adenoviruses 5- Papovaviruses e 2- Poxviruses (smallpox v.) e.g. Human papilloma virus(HPV): cervical cancer e 3- Herpesviruses 6- Polyomaviruses (JC & BK) e 4- Hepadnaviruses (HBV) 7- Parvovirus Lec. (8) D./ Maha E. Omran 28 Name: Adeno viruses (> 41 serotypes) Disease: pharyngitis , pneumonia/ conjunctivitis/ acute infantile gastroenteritis Mode of transmission: Droplet, inhalation / contact / 4F Lab. Diagnosis: Detection of adenovirus antigen in: A: Specimen nasopharyngeal or throat swabs, B: Diagnostic test conjuctival swabs or faeces. Treatment: No specific antiviral therapy Prevention: Sanitary conditions live vaccine as coated gelatin capsules for new military persons. 29 Lec. (7) D./ Maha E. Omran Pox viruses ▸ Poxviruses are the largest viruses known. ▸ Three medically important: smallpox (variolla v.) ‫الجدري‬, vaccinia v., molluscum contagiosum v. ▸ Poxviruses of animal origin, such as cowpox, monkeypox. ▸ They are named for the skin lesions “pocks” that they cause. ▸ Smallpox is a contagious = easily transmitted, disfiguring ‫ يُسبب تشوهات‬and often deadly disease. ▸ The only human disease that has been eradicated. Lec. (7) D./ Maha E. Omran 30 ▸ Naturally occurring smallpox was finally eradicated worldwide in the 1978 — the result of successful global immunization campaign launched by WHO. But the virus didn't disappear entirely, stocks of smallpox virus, set aside for research purposes, are officially stored in two high-security labs — one in the United States and one in Russia. This has lead to concerns that smallpox someday may be used as a biological warfare agent. Lec. (7) D./ Maha E. Omran 31 G.R. Smallpox was successfully eradicated. 1. It has a single stable serotype. 2. No animal reservoir (infect only human). 3. No carrier state. 4. Easily recognized clinically. 5. Global immunization campaign. 6. Prompt antibody response. Lec. (7) D./ Maha E. Omran 32 Herpesviruses ▸ Three subfamilies: ▹ Alphaherpesviruses - HSV-1, HSV-2, VZV ▹ Betaherpesviruses - CMV, HHV-6, HHV-7 ▹ Gammaherpesviruses - EBV, HHV-8 ▸ Set up latent infection following primary infection. Lec. (7) D./ Maha E. Omran 33 ▸ Reactivation are more likely to take place during periods of immunosuppression [by any stimuli] e.g., common cold, stress, sunlight, menstruation, …etc. ▸ Both primary infection and reactivation are likely to be more serious in immuno- compromised patients. Lec. (7) D./ Maha E. Omran 34 Name: Herpes simplex v. (HSV-1, HSV-2) Disease: Primary infection then Reactivation: see later Mode of 1.Contact (v. is shed in saliva, tears) / transmission: 2. Sexually (v. is shed in genital secretions)& 3. during delivery (infected birth canal). Lab. Diagnosis: -Electron microscopy of vesicle fluid. A: Specimen -Tzank smear: cells from the base of the vesicle are stained B: Diagnostic test with Giemsa stain, revealing multinucleated giant cells. -PCR: for diagnosis of herpes simplex encephalitis. -Isolation in tissue culture./ Serology Treatment: Acyclovir (IV, oral, cream, ophthalmic ointment) Famciclovir and valacyclovir (oral only) Prevention: Avoid contact with vesicular lesion or ulcer. Cesarean section can prevent neonatal herpes. 35 Lec. (7) D./ Maha E. Omran Pathogenesis ▸ During the primary infection, HSV replicates in the skin or mucous membrane at the initial site of infection, migrates up the neuron and becomes latent in the ganglia. ▸ Upon reactivation, it migrates down from ganglia to the skin, replicates causing lesions. Lec. (7) D./ Maha E. Omran 36  Clinical Manifestations ▸ Oral-facial Herpes caused by HSV-1 1- Acute Gingivostomatitis (primary) ▹ Occurs primarily in children, characterized by fever, irritability and vesicular rash (lesion, ulcers) in mouth with pain and bleeding of the gums. Neck glands are commonly enlarged. ▹ Usually a self limiting disease which lasts around 2-3 weeks. ▹ Many children have asymptomatic primary infections. Lec. (7) D./ Maha E. Omran 37 2- Herpes labialis (cold sore) ▹ It is the reactivation of oral HSV. ▹ A prodrome of tingling, warmth or itching at the site usually proceeds the recurrence. About 12 hours later, redness appears followed by papules and then vesicles. 3- Ocular Herpes (keratoconjunctivitis) (reactivation) ▸ HSV causes a broad spectrum of ocular disease, ranging from mild superficial lesions involving the external eye, to severe sight-threatening diseases of the inner eye (scaring 38 & blindness). Lec. (7) D./ Maha E. Omran Clinical Manifestations caused by HSV-2 ▸ 1- Genital Herpes Genital lesions may be primary or recurrent. ▸ 2- Neonatal herpes (primary) By contact with vesicular lesions or sometimes (asymptomatic shedding of HSV-2) within the birth canal. It varies from severe (encephalitis) to mild (local lesions on skin, eyes, mouth) to asymptomatic. Lec. (7) D./ Maha E. Omran 39  Name: Varicella- Zoster Virus (VZV) Disease: Primary infection: Varicella “chickenpox” ‫الجديري المائي‬ Reactivation: Zoster “shingles” ‫الحزام الناري‬ Neonatal varicella Mode of Respiratory droplet and direct contact with lesions (highly transmission: contagious). / vertical transmission Lab. Diagnosis: Clinically Treatment: No antiviral therapy is necessary for immunocompetent children. - Acyclovir, valacyclovir, famciclovir (for adults) as it reduces duration and severity of symptoms, reduce post-herpetic neuralagia. Prevention: 1. Zoster immunoglobulin (ZIG) should be given to: -susceptible pregnant women who had contact with suspected cases of varicella. -infants whose mothers develop varicella during the last 7 days of pregnancy or the first 14 days after delivery. Lec. (7) 2. A live attenuated vaccine is available (to be given > 1 year old). 40 D./ Maha E. Omran  Pathogenesis Lec. (7) D./ Maha E. Omran VZV infects the mucosa of the upper respiratory tract spreads via blood to the skin vesicular rash (varicella) virus remains latent in the ganglia Later in life, frequently at times of the virus reactivates in the reduced cellular immunity ganglion tracks down the sensory nerve to the area of the skin innervated by the nerve producing vesicular rash and nerve pain of (zoster). 41  Clinical Picture 1- Varicella ▸ Incubation period of 14-21 days. ▸ fever, malaise, a widespread vesicular rash in crops on trunk then spread to head and extremities (papule, vesicle, pustule, crust). ▸ Itching. ▸ Mild in children, more severe in adults. Lec. (7) D./ Maha E. Omran 42 Complications ▸ Complications are rare (pneumonia & encephalitis) but occurs more frequently and with greater severity in adults and immunocompromised patients. ▸ Most common complication is secondary bacterial infection of the vesicles. Lec. (7) D./ Maha E. Omran 43 2- Zoster (Shingles) ▸ It may occur at any age but the vast majority of patients are more than 50 years of age. ▸ Occurrence of painful vesicles along the sensory nerve of the head or trunk. Pain lasts for weeks (post-herpetic neuralgia). 3- Neonatal Varicella ▸ VZV can cross the placenta in the late stages of pregnancy to infect the fetus congenitally. ▸ Neonatal varicella may vary from a mild disease to a fatal disseminated infection. Lec. (7) D./ Maha E. Omran 44  Lec. (7) D./ Maha E. Omran Smallpox vs. Chickenpox Item Small pox Chicken pox Severity and location of Severe, centrifugal Superficial, trunk lesions distribution Types of lesions Combination of All are the same scabs, vesicles, stage pustules Timing of infection After signs & In I.P. Transmission symptoms till scabs fall Severity of the disease Fatal (deadly) Mild childhood disease 45 46