1.2. Basic Virology 2024.pdf

General/Basic Virology Associate Professor Dr. Thu Zar Han  Learning Outcomes The student will be able to: 1.Describe the structures of viruses. 2.Classify the medically important viruses. 3.Describe different modes of transmission of viral infection. 4.List the steps in th...

General/Basic Virology Associate Professor Dr. Thu Zar Han  Learning Outcomes The student will be able to: 1.Describe the structures of viruses. 2.Classify the medically important viruses. 3.Describe different modes of transmission of viral infection. 4.List the steps in the replication cycles of viruses and the outcome of viral infections. 5.Outline the different laboratory tests to diagnose viral infection. 6.Outline the preventive strategies for viral infections. General Properties of Viruses Smallest infectious agents Obligate intracellular parasite Size : 20 – 300nm in diameter Contains one kind of nucleic acid (RNA or DNA) Nucleic acid is encased in a protein coat (capsid) Capsid may be surrounded by a lipid-containing membrane (envelope) The entire infectious unit is termed a virion  Virion Complete infectious virus particle Nucleocapsid : adeno viruses polio viruses Nucleocapsid plus a surrounding envelope : herpes viruses orthomyxoviruses  Defective Virus Functionally deficient in some aspect of replication Require help of another virus e.g. HBV : helper virus HDV : defective virus Interfere the replication of normal viruses  Viroids A single molecule of circular RNA Without a protein coat or envelope Cause diseases of PLANTS  Prions Contains protein only. No nucleic acid Proteinaceous infectious agent Normal protein converts to pathologic prion form due to post-translational modification Cause slow disease in animals & and human  1. Virus genomic materials/ Nucleic Acid Either DNA or RNA; SS or DS, haploid or diploid; circular or linear; segmented or non segmented; + or - sense/polarity  Virus genomic materials parvo all all reo/rota/bunya  DNA Viruses Enveloped Nonenveloped dsDNA dsDNA ssDNA Poxviruses Adenoviruses Parvoviruses Herpesviruses Papillomaviruses Hepadnavirus Polyomaviruses AP4H2  RNA Viruses Enveloped Nonenveloped +ssRNA encode RT ssRNA Retroviruses +ssRNA dsRNA Non-segmented Segmented Picornaviruses Reoviruses (segmented) Paramyxoviruses Caliciviruses Arenaviruses (-ssRNA) Bunyaviruses Rhabdoviruses Astroviruses (-ssRNA) Orthomyxoviruses Filoviruses (-ssRNA) Hepeviruses Coronaviruses (+ssRNA) Flaviviruses Transmitted by ingestion (-ssRNA) (+ssRNA) Togaviruses (+ssRNA) Three symmetry 2. Protein capsid 1. Cubical / icosahedral symmetry 2. Helical symmetry 3. Complex symmetry Functions of capsid proteins 1. Protect the nucleic acid from degradation by nucleases. 2. Attachment of the virus to specific receptors on the host cell surface. 3. Important antigens elicit Abs 4. Serotypes  1. Cubic symmetry Capsomers are arranged in 20 triangles forming a symmetric figure(icosahedron) with the outline of a sphere. Naked or enveloped virus Poliovirus Herpesvirus Adenovirus  2. Helical symmetry Capsomeres are bound to nucleic acid winding it into a helix Hollow coil as rod-shaped. No naked helical viruses Rabies virus  3. Complex structure More complicated structure eg, brick-shaped  3. Viral Envelope A lipoprotein membrane composed of lipid derived from the host cell membrane and protein that is virus-specific. Spike/projections (peplomers): viral origin Instability of virus : Contains lipid (sensitive to lipid solvent, ether/bile)  Applications of virus structure Classification Surface protein responsible for attachment to host cell receptors → tissue specificity, host specificity Detect Nucleic acid by PCR/RT PCR (qualitative/quantitative) Detect capsid protein, envelope protein or surface glycoprotein spikes protein by serological tests Target for antiviral therapy Viral protein can be used as a vaccine antigen  Applications of virus structure Classification Surface protein responsible for attachment to host cell receptors → tissue specificity, host specificity (pathogenesis) Detect Nucleic acid by PCR/RT PCR (qualitative/quantitative) (diagnosis) Detect capsid protein, envelope protein or surface glycoprotein spikes protein by serological tests (diagnosis) Target for antiviral therapy (treatment) Viral protein can be used as a vaccine antigen (prevention)  Structure Classification of viruses Modes of transmission Replication Pathogenesis and outcome of viral infection Laboratory diagnosis Treatment, prevention and control of viral infection  Classification of Viruses Nucleic acid composition Morphology of protein capsid Modes of transmission Host tissue and cell tropisms Symptomatology  Modes of transmissions Ingestion Polioviruses Hepatitis A virus (HAV) Hepatitis E virus (HEV) Reo/rota virus  Modes of transmissions Transfusion Human immunodeficiency virus (HIV) Hepatitis B virus (HBV) Hepatitis C virus (HCV) Cytomegalovirus (CMV)  Modes of transmissions Sexual Human immunodeficiency virus (HIV) Hepatitis B virus (HBV) Herpes simplex virus 2 (HSV 2) Human papilloma virus (HPV)  Modes of transmissions Mother to child (vertical transmission) (HIV, HBV, CMV, Rubella) Vector borne (dengue, yellow fever, JBE) Zoonotic viral infections (rabies, MERS)  Host and tissue/cell tropisms Host : human, animal, plant, bacteria Tissue : Neurotropic viruses (Rabies , polioviruses) Hepatotropic viruses (HAV, HBV, HCV, HDV, HEV)  Structure Classification of viruses Modes of transmission Replication Pathogenesis and outcome of viral infection Laboratory diagnosis Treatment, prevention and control of viral infection Adsorption/ attachment Viruses Site of Exception replication Most DNA viruses Nucleus Poxvirus Most RNA viruses cytoplasm HIV, Influenza virus  Structure Classification of viruses Modes of transmission Replication Pathogenesis and outcome of viral infection Laboratory diagnosis Treatment, prevention and control of viral infection  Viral Pathogenesis Pathogenesis = the manner of development of a disease 1. Entry and primary replication (lymph nodes, blood – viremia: primary and secondary) 2. Viral spread and cell tropism 3. Cell injury and clinical illness 4. Recovery from infection 5. Virus shedding Mechanisms of spread of virus through the body in human viral infections Viral Persistence: Chronic and Latent Infections 1. Carrier state refers to people who produce virus for long periods of time and can serve as a source of infection for others. Example: hepatitis C virus (HCV) infection 2. Latent infections are those infections that are not producing virus at the present time but can be reactivated at a subsequent time. Example: herpes virus infections (HSV, VZV) 3. Slow virus infections refer to those diseases with a long incubation period, often measured in years. Eg: SSPE, Progressive multifocal leukoencephalopathy (PMLE) Effect of Virus Infection on Cells  Structure Classification of viruses Modes of transmission Replication Pathogenesis and outcome of viral infection Laboratory diagnosis Treatment, prevention and control of viral infection  Specimen Collection Transportation: All specimen for virus isolation must be sent by cold chain (in ice) All swabs must be in viral transport medium (VTM) Transportation of Specimen  Laboratory diagnosis of viral infections 1. Electron Microscopy 2. Viral Culture 3. Antigen detection 4. Nucleic acid detection 5. Antibody detection  Lab diagnosis of viral infection 1 Electron microscopy + 2 Culture + 3 Antigen detection +++ 4 Antibody detection +++ 5 Nucleic acid detection ++ PCR/ NA probe Qualitative (Presence /absence) Quantitative (viral load)  1. Microscopy 1. Electron microscopy : determine virus size and shape 2. Fluorescent microscope: fluorescent Abs 3. Light microscope : Inclusion bodies, multinucleated giant cells IB formation: virus accumulation at the site of assembly, larger than virus particle (seen by light microscope)  2. Cultivation of Viruses Obligate intracellular parasite Cannot grow in cell-free media Cultivated in 1. Tissue cultures & cell cultures 2. Developing chick embryo (DCE)/ fertile egg 3. Living animals  Cell Culture Primary cultures- trypsin-treated host cells Secondary cultures- diploid cell line Continuous cell lines – from malignant tissues Cultivation of Viruses in DCE (Fertile egg) Growth of virus Detection of virus-infected cells Negri bodies: intracytoplasmic IB caused by rabies Owl eye intranuclear IB in CMV- virus in brain tissue infected cell  Structure Classification of viruses Modes of transmission Replication Pathogenesis and outcome of viral infection Laboratory diagnosis Treatment, prevention and control of viral infection  Prevention & control General prevention 4 F (food, finger, fly, feces) sterilization & disinfection condom, face mask handwashing health education Specific prevention Chemoprophylaxis & chemotherapy Immunoprophylaxis & immunotherapy  Treatment of viral infection Antiviral chemotherapy Selectively inhibit viral function without damaging the host Target of antiviral drugs- stage of viral replication SARS CoV-2  Viral vaccines (Immunoprophylaxis) Killed-virus vaccine: rabies vaccine Salk polio vaccine Attenuated live-virus vaccine : OPV MMR (mumps, measles, rubella vaccine) Recombinant vaccine : Hepatitis B vaccine mRNA vaccine: Pfizer-BioNTech COVID-19 vaccine (Comirnaty®) Moderna COVID-19 vaccine (Spikevax™)  Antisera / Specific immunoglobulin (Immunotherapy) Post exposure prophylaxis Human Hepatitis B immunoglobulin (HBIG) Human rabies immunoglobulin (HRIG)  Prescribed Textbooks 1. Levinson, W. (2016). Review of medical microbiology and immunology. (14th ed.). United States of America: The McGrew Hill Companies 2. Brooks, G.F., Carroll, K.C., Butel, J.S., Morse, S.A. and Meitzner, T.A. (2016). Jawetz, Melnick and Adelberg's medical microbiology. (27th ed).United States of America: The McGrew Hill Companies.  Prescribed text book Reliable web source (WHO, CDC) Short video clip from YouTube Images of diseases Case scenario