Lecture 4 - General Properties Of Viruses And Pathogenesis PDF

Classification of Viruses Viroids, Prions  Viral Properties Viruses are inert (nucleoprotein ) filterable agents. Viruses are obligate intracellular parasites Viruses cannot make energy or proteins independent of a host cell. Viral genome are RNA or DNA but not both...

Classification of Viruses Viroids, Prions  Viral Properties Viruses are inert (nucleoprotein ) filterable agents. Viruses are obligate intracellular parasites Viruses cannot make energy or proteins independent of a host cell. Viral genome are RNA or DNA but not both. Viruses have a naked capsid or envelope with attached proteins. Viruses do not have the genetic capability to multiply by division.  General Morphology Helical Viruses – Ebola Polyhedral Viruses – icosahedron shape Enveloped Viruses – Influenza, Human Herpes Virus Complex Viruses - Bacteriophages DNA Viruses RNA Viruses  CLASSIFICATION OF VIRUSES basis of classification Virion morphology Virus genome properties Virus protein properties Antigenic properties Physicochemical properties Biological properties  Virion The complete infectious unit of virus particle Structurally mature, extracellular virus particles. Novel Coronavirus SARS CoV 2 Virion structure envelope Capsid Viral core  Viral Capsid The protein shell, or coat, that encloses the nucleic acid genome. Functions: a. Protect the viral nucleic acid. b. Participate in the viral infection. c. Share the antigenicity.  Nucleocapsid The core of a virus particle consisting of the genome plus a complex of proteins. complex of proteins = Structural proteins +Non- Structural proteins (Enzymes &Nucleic acid binding proteins) viruses can be divided into 2 kinds: enveloped virus and naked virus.  Properties of naked viruses Stable in hostile environment Not damaged by drying, acid, detergent, and heat Released by lysis of host cells Can sustain in dry environment Can infect the GI tract and survive the acid and bile Can spread easily via hands, dust, fomites, etc Can stay dry and still retain infectivity  Envelope A lipid-containing membrane that surrounds some viral particles. It is acquired during viral maturation by a budding process through a cellular membrane, Viruses-encoded glycoproteins are exposed on the surface of the envelope. Properties of enveloped viruses Labile in dry Damaged by drying, acid, detergent, and heat Pick up new cell membrane during multiplication Insert new virus-specific proteins after assembly Virus is released by budding SARS-CoV-2 Structure  Clinical findings Common colds: Incubation period: 2-5 days Symptoms: nasal discharge, malaise, pneumonia may occur. Wheezing attacks among asthmatic children. 2002 SARS 2012 MERS 2019 COVID19  Novel Coronavirus SARS CoV-2 People with COVID-19 have had a wide range of symptoms reported – ranging from mild symptoms to severe illness. Symptoms may appear 2-14 days after exposure to the virus. People with these symptoms or combinations of symptoms may have COVID-19: Cough Shortness of breath or difficulty breathing Or at least two of these symptoms: Fever Chills Repeated shaking with chills Muscle pain Headache Sore throat New loss of taste or smell Children have similar symptoms to adults and generally have mild illness. ACE2 receptors Mutations  Diagnosis and Treatment PCR Antigen U.S. Food and Drug Administration approved the antiviral drug Remdesivir for use in adult and pediatric patients 12 years of age and older for the treatment of COVID-19 requiring hospitalization. Pfizer’s Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and pediatric patients 12 years of age and older. Vaccines Human Diseases Associated with B19 Parvovirus Erythema Infectiosum (Fifth Disease)  Clinical Findings Joints in the hands and the knees are most frequently affected. Mimic rheumatoid arthritis, and the arthropathy may persist for weeks, months, or years. Incubation period - 1–3 weeks Symptoms are flu-like, including fever, malaise, myalgia, chills and itching. The illness is short-lived, with the rash fading after 2–4 days, although the joint symptoms may persist longer. Specific IgG antibodies appear about 15 days postinfection.  Treatment Fifth disease and transient aplastic crisis are treated symptomatically. Commercial immunoglobulin preparations contain neutralizing antibodies to human parvovirus. Prevention and Control There is no vaccine against human parvovirus. Good hygienic practices, such as hand washing and not sharing drinks, should help prevent the spread of B19. ADENOVIRUS INFECTIONS IN HUMANS Respiratory Diseases (Pneumonia) Eye Infections (“swimming pool conjunctivitis” - types 3 and 7; epidemic keratoconjunctivitis - types 8, 19, and 37) Gastrointestinal Disease (gastroenteritis – types 40, 41) Other Diseases (Adenoviral infections after organ transplantation; hemorrhagic cystitis in children, types 11, 21)  Epidemiology Adenoviruses are spread: by direct contact by the fecal–oral route by respiratory droplets by contaminated fomites hand-to-eye transfer (eye infection) Treatment There is no specific treatment for adenovirus infections. Prevention and Control Hand washing, disinfection, chlorination of swimming pools, sterilization of equipment  Herpes Virus It’s a kind of enveloped DNA virus. Icosahedral core surrounded by a lipoprotein envelope. linear double-stranded DNA. Large (120–200 nm in diameter), second in size only to poxviruses. Capsid surrounds DNA core and over the capsid is tegument (a protein-filled region). Nuclear membrane derived lipid bilayer containing viral  Classification Eight human herpesvirus species are known. – Herpes Simplex Virus type 1 (HSV-1) – Herpes Simplex Virus type 2 (HSV-2) – Varicella-Zoster Virus (VZV) – Cytomegalovirus (CMV) – Epstein-Barr Virus (EBV) – Human Herpes Virus type 6 (HHV-6) – Human Herpes Virus type 7 (HHV-7) – Human Herpes Virus type 8 (HHV-8)  Clinical Findings: HSV-1 Causes several forms of primary and recurrent disease. Gingivostomatitis – Occurs primarily in children and is characterized by fever, irritability and vesicular lesions in the mouth. – The primary disease is more severe and lasts longer than recurrences. – The lesions heal spontaneously in 2 to 3 weeks. – Many children have asymptomatic primary infections Herpes labialis – fever blisters or cold sores is the milder, recurrent form – characterized by crops of vesicles, usually at the mucocutaneous junction of the lips or nose – Recurrences frequently reappear at the same site.  Clinical Findings: HSV-1 Keratoconjunctivitis – characterized by corneal ulcers and lesions of the conjunctival epithelium. – Recurrences can lead to scarring and blindness Encephalitis – necrotic lesion in one temporal lobe. – Fever, headache, vomiting, seizures, and altered mental status  Treatment Acyclovir : treatment of choice – shortens the duration of the lesions – reduces the extent of shedding of the virus Penciclovir (a derivative of acyclovir) or docosanol: recurrences of orolabial HSV-1 Valacyclovir and famciclovir: genital herpes and in the suppression of recurrences.  Varicella-Zoster Virus (VZV) Clinical chicken pox (primary infection) 90% of cases before age 10, peak incidence 2- 8 years Virus entry through inhalation Replicates in respiratory tract and invades lymph nodes. Viremia: spreads virus to target organs Incubation period 14-18 days VZV - Chicken Pox  Epstein-Barr Virus (EBV) Structure: DNA virus, enveloped Etiologic agent of infectious mononucleosis and African Burkitt’s Lymphomas. Recent study has linked with Hodgkins lymphoma Cultured in only lymphoblastoid cell lines derived from B lymphocytes of humans and higher primates.  Epstein-Barr Virus (EBV) EBV nuclear antigens (EBNAs) appear in the nucleus prior to virus directed protein synthesis. Viral capsid antigen (VCA) is detected in virus producing cell lines EBV can be cultured from saliva and thus infection is acquired by contact. Transmission – contact with infected secretions, – low contagiousness, – virus can be cultured from throat washings  EBV: Clinical Features Infectious mononucleosis, usually asymptomatic If symptoms persist (young adults) – low fever – headache, – sore throat, – fatigue, – night chills (sweats), – enlarged lymph nodes and spleen, – elevated lymphocytes and monocytes and atypical lymphocytes Complications – laryngeal obstruction, meningitis, – encephalitis, hemolytic anemia, – thrombocytopenia or splenic rupture may BURKITT’S occur in 1 to 5% of the patients LYMPHOMA General Structure Enveloped Viral genome is linear, negative sense ss RNA. Non-segmented genome, all members are antigenically stable. Haemagglutinin glycoprotein HN proteins are important for viral attachment.  Measles (Rubeola) Virus Measles is an acute, highly infectious disease characterised by fever, respiratory symptoms and maculopapular rash. Complications are common. Although there is a vaccine, incidence is low, but still a leading cause of death in young children in developing countries. Humans are the only host. Other animals can be experimentally infected.  Pathogenesis Rash appears at about day 14, just as circulating Antibodies is detectable, viraemia disappears and fever falls. Rash develops as a result of interaction of immune T cells with virus-infected cells in the small blood vessels and lasts about 1 week. Brain/CNS infection is common. Complication 🡪 subacute sclerosing panencephalitis (SSPE) that develops years after infection, caused by viruses remaining in the body.  Clinical Findings Fever, sneezing, coughing, running nose and redness of eyes; Koplik’s spots (small bluish-white ulcerations on the buccal mucosa opposite lower molars). Rash starts on head, spreads to the chest, trunk, lower limbs. Pneumonia – most common life-threatening complications of measles. More serious complications 🡪 acute encephalitis Subacute sclerosing panencephalitis occur insidiously 5-15 yrs after case of measles, characterised by progressive mental deterioration, involuntary movements, muscular rigidity and coma. MEASLES - Koplik’s spots ¬ Arthropod-borne viruses (arboviruses) are viruses that can be transmitted to man by arthropod vectors. ¬ They can multiply in the tissues of the arthropod withoutevidence of disease or damage. ¬ The vector acquires a lifelong infection through the ingestion of blood from a viremic vertebrate. ¬ All arboviruses have an RNA genome, and most have a lipid-containing envelope and consequently are inactivated by ether or sodium deoxycholate. ¬ Inclusion in this group is based on ecological and epidemiological considerations and hence it contains viruses of diverse physical and chemical properties.  General Properties The arboviruses share some common biological properties 1. All members produce fatal encephalitis in suckling mice after intracerebral inoculation. 2. They possess haemagglutinin and agglutinate erythrocytes of goose or day-old chicks. 3. In general, arboviruses are readily inactivated at room temperature and by bile salts, ether and other lipid solvents  Arthropod Vectors Mosquitoes Japanese encephalitis, dengue, yellow fever, Rift valley fever St. Louis encephalitis, Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), Venezuelan Equine Encephalitis (VEE), etc. Ticks Crimean-Congo haemorrhagic fever, Kyasanur forest disease and various tick-borne encephalitis etc. Sandflies Sicilian sandfly fever  Examples of Arthropod Vectors Aedes aegyti Ixodid Ticks Culex Mosquito Phlebotomine Sandfly  Animal Reservoirs In many cases, the actual reservoir is not known. The following animals are implicated as reservoirs Birds Japanese B encephalitis, St Louis encephalitis, EEE, WEE Pigs Japanese B encephalitis Monkeys Yellow Fever Rodents VEE, Russian Spring-Summer encephalitis  Pathogenesis When an infected vector bites a suitable host, the virus is injected into the capillary circulation. Virus comes in contact with susceptible target cells such as endothelial cells of capillaries, monocytes, macrophages. After replication in endothelial cells and reticuloendothelial cells, a secondary viraemia usually results leading to infection of target organs such as brain, skin, musculature and liver. The virus reaches the brain by infecting small blood vessels of the brain. Influenza virus Influenza viruses ssRNA, negative sense genome, 7-8 segments, 10 genes spherical enveloped – Hemagglutinin – Neuraminidase Viral Structure Zanamivir/Oseltamivir Adamantanes  Classification Antigenic differences exhibited by two of the internal structural proteins: nucleocapsid (NP) and matrix (M) proteins, are used to divide influenza viruses into types A,B,C. NP antigens are stable and exhibit no serologic cross reactivity. Surface glycoproteins: HA and NA, are used to subtype the viruses. These two antigens are variable. These Ags are responsible for immunity to infection. So far, 15 subtypes for HA (H1-H15); and 9 subtypes for NA (N1-N9) have been recovered from birds, animals and humans. In humans, there are 4 HA (H1-3,H5) and 2 NA (N1-2).  Distribution of HA serotypes in nature HA serotype Birds Horses Pigs Humans HA1 yes yes yes HA2 yes yes HA3 yes yes yes yes HA4 yes HA5 yes yes HA6 yes HA7 yes yes HA8-15 yes Distribution of N serotypes in nature Birds Horses Pigs Humans N1 yes yes yes N2 yes yes yes N3 yes N4 yes N5 yes N6 yes N7 yes yes N8 yes yes N9 yes  Antigenic Drift & Shift Antigenic variants confer selective advantage over the parental virus in the presence of Ab against the original strain. The 2 surface Ags undergo antigenic variation independent of each other. Antigenic drift = Minor changes, a gradual change in antigenicity due to point mutations that affect major antigenic sites on the glycoprotein. Antigenic shift = Major changes, an abrupt change due to genetic reassortment with an unrelated strain, which results in the appearance of a new subtype.  Human Cancer Viruses At least 15% of all human tumors worldwide have a viral cause. two of great significance worldwide—cervical cancer and liver cancer. Viruses associates with cancers: - human papillomaviruses - Epstein-Barr virus - Human herpesvirus 8 - Hepatitis B virus, hepatitis C virus - Two human retroviruses  Human Cancer Associated with Viruses Human papillomaviruses – Genital tumors – Squamous cell carcinoma – Oropharyngeal carcinoma Epstein-Barr virus – Nasopharyngeal carcinoma – Burkitt's lymphoma – Hodgkin's disease – B cell lymphomas Human herpesvirus 8 - Kaposi's sarcoma Hepatitis B virus - - Hepatocellular carcinoma Human T-lymphotropic virus - Adult T cell leukemia Human immunodeficiency virus - AIDS-related malignancies Hepatitis C virus - Hepatocellular carcinoma  Classification DNA tumor viruses RNA tumor viruses ▪ papilloma- ▪ Human T-cell Leukemia virus ▪ polyoma- ▪ Hepatitis C virus ▪ adeno- ▪ herpes- ▪ hepadna- ▪ poxvirus  Multistep Carcinogenesis Carcinogenesis is a multistep process Multiple genetic changes must occur to convert a normal cell into a malignant one. Tumors usually develop slowly over a long period of time. Multistep process of cellular evolution involves: - cellular genetic instability - mutations - activation of multiple cellular oncogenes and inactivation of tumor suppressor genes. - tumor virus usually acts as a cofactor, providing only some of the steps required to generate malignant cells. Viruses are necessary—but not sufficient—for development of tumors with a viral etiology.  Isolation, Cultivation, and Identification of Viruses Growing Bacterial Viruses in the Laboratory A bacteriophage sample is mixed with host bacteria and melted agar. The agar containing the bacteriophages and host bacteria is then poured into a Petri plate The virus-bacteria mixture solidifies into a thin top layer. Each virus infects a bacterium, multiplies, and releases several hundred new viruses. Presence of clearings, or plaques, visible against a lawn of bacterial growth on the surface of the agar indicated the destruction of bacterial cells. While the plaques form, uninfected bacteria elsewhere in the Petri plate multiply rapidly and produce a turbid background. The concentrations of viral suspensions measured by the number of plaques are usually expressed in terms of plaque-forming units (PFU).  Growing Animal Viruses in the Laboratory In Living Animals Embryonated eggs Cell cultures  Viral Identification Most commonly Serological method. The virus is detected and identified by its reaction with antibodies. Restriction fragment length polymorphisms (RFLPs) PCR Viral Multiplication  Replication of Viruses Attachment Penetration Uncoating Expression of Viral Genomes Synthesis of Viral Components Morphogenesis and Release  Multiplication of Animal Viruses Attachment Attachment sites Many of the enveloped viruses, such as influenza virus, the attachment sites are spikes located on the surface of the envelope. Receptor sites are proteins of the host cell.  Multiplication of Animal Viruses Entry Many viruses enter into eukaryotic cells by receptor-mediated endocytosis. Enveloped viruses can enter by an alternative method called fusion, in which the viral envelope fuses with the plasma membrane and releases the capsid into the cell’s cytoplasm.  Multiplication of Animal Viruses Uncoating Uncoating is the separation of the viral nucleic acid from its protein coat. Some animal viruses accomplish uncoating by the action of lysosomal enzymes of the host cell. These enzymes degrade the proteins of the viral capsid. Replication of a DNA Virus  Replication of a RNA-Containing Virus The replication cycle occurs in the cytoplasm. (1) The virus enters the cell and the viral RNA genome is uncoated. (2) As a positive-sense, single-stranded genome, the RNA is directly translated, producing viral proteins. (3) A negative-sense RNA copy of the positive template is synthesized. (4) It is used to produce many positive-sense copies. (5) The newly synthesized positive-sense RNA molecules are assembled with viral structural proteins to produce new progeny virions. Maturation and Release  MODES OF TRANSMISSION OF VIRUSES Direct transmission from person to person by contact - droplet or aerosol infection (eg, influenza, measles, smallpox); - by sexual contact (eg, papillomavirus, hepatitis B, herpes simplex type 2, human immunodeficiency virus); - by hand–mouth, hand–eye, or mouth–mouth contact (eg, herpes simplex, rhinovirus, Epstein-Barr virus); - by exchange of contaminated blood (eg, hepatitis B, human immunodeficiency virus). Indirect transmission by the fecal–oral route (eg, enteroviruses, rotaviruses, infectious hepatitis A) Transmission from animal to animal, with humans an accidental host (eg, arenaviruses, hantaviruses). Transmission by means of an arthropod vector (eg, arboviruses, now classified primarily as togaviruses, flaviviruses, and bunyaviruses).  PREVENTION AND TREATMENT OF VIRAL INFECTIONS Antiviral Chemotherapy – Nucleoside and Nucleotide Analogs – Reverse Transcriptase Inhibitors – Protease Inhibitors Interferons Viral Vaccines – Killed-Virus Vaccines – Attenuated Live-Virus Vaccines  Viroids Viroids are small infectious agents that cause diseases of plants. They are nucleic acid molecules without a protein coat. Plant viroids are single-stranded, covalently closed circular RNA molecules consisting of about 360 nucleotides. Viroid RNA does not encode any protein products; the devastating plant diseases induced by viroids occur by an unknown mechanism.  Prions Prions are infectious particles composed solely of protein with no detectable nucleic acid. They are highly resistant to inactivation by heat, formaldehyde, and ultraviolet light that inactivate viruses. The prion protein is encoded by a single cellular gene. Prion diseases, mad cow disease in cattle, and kuru and Creutzfeldt-Jakob disease in humans. References Jawetz, Medical Micriobiology, 26th Edition. Chapter 29 Gerard J. Tortora, Berdell R. Funke, Christine L. Case - Microbiology_ an introduction-Pearson (2018), Chapter 13