Medical Virology Semester 3 Crash Revision — OmpathStudy

SECTION 1: FOUNDATIONS, ANTIVIRALS, VACCINES & DNA VIRUSES A. INTRODUCTION TO VIRUSES A virus is an obligate intracellular parasite — has no ribosomes, no independent metabolic machinery, cannot generate its own ATP, and therefore cannot replicate outside a living host cell Composed minimally of: genome (DNA or RNA, never both) + capsid (protein coat protecting the genome) ± envelope (lipid bilayer stolen from host membrane, studded with viral glycoproteins) The unit of a fully assembled, infectious virus particle is called a virion Viruses are acellular — this is the core distinction from bacteria/fungi/parasites, which are cellular B. CLASSIFICATION OF VIRUSES 1. ICTV system (structural/taxonomic) Hierarchy: Order → Family → Subfamily → Genus → Species Formed and maintained by the International Committee on Taxonomy of Viruses — standardizes naming so research globally uses the same nomenclature 2. Baltimore Classification (by genome type + replication strategy) — the exam favorite Class I — dsDNA: Herpesviruses, Adenovirus, Poxvirus, Papillomavirus Class II — ssDNA: Parvovirus Class III — dsRNA: Rotavirus Class IV — (+)ssRNA: Picornaviruses (polio, coxsackie, rhino), Togavirus (rubella), Flavivirus (yellow fever, dengue, Zika), Coronavirus Class V — (−)ssRNA: Orthomyxovirus (influenza), Paramyxovirus (measles, mumps, RSV), Rhabdovirus (rabies), Filovirus (Ebola, Marburg) Class VI — ssRNA-RT (Retrovirus): HIV Class VII — dsDNA-RT: Hepatitis B Why examiners love this: genome type predicts replication site and enzymes needed. (+)ssRNA genome = acts directly as mRNA, fastest to replicate. (−)ssRNA must first be transcribed to (+)RNA by a virus-carried RNA-dependent RNA polymerase before translation can happen. Retroviruses carry reverse transcriptase to convert RNA→DNA before integration. C. VIRUS STRUCTURE Capsid symmetry: icosahedral (most viruses — efficient packing), helical (rabies, influenza, paramyxoviruses), complex (poxvirus — brick-shaped, no clear symmetry) Enveloped viruses: fragile, destroyed by heat/drying/detergents/bile/gastric acid → transmitted via blood, sexual contact, respiratory droplets, organ transplant — need close contact, don't survive well outside host Non-enveloped (naked) viruses: tough, resistant to drying, detergents, and gut pH → transmitted via faecal-oral route, fomites, survive long on surfaces and in water D. ATYPICAL INFECTIOUS AGENTS Prions — no nucleic acid at all; infectious misfolded protein (PrP^Sc) that converts normal PrP^C into the misfolded form; cause spongiform encephalopathies (CJD, kuru); resistant to standard sterilization (autoclaving, formalin) Viroids — small circular ssRNA, no capsid, infect plants only Satellite viruses — defective, require a helper virus to replicate. Classic exam example: Hepatitis D requires Hepatitis B as helper (HDV uses HBV's surface antigen as its envelope) Slow viruses — long incubation, slowly progressive disease: HIV, prions, and SSPE (subacute sclerosing panencephalitis — a late, fatal complication of measles years after infection) E. VIRAL REPLICATION CYCLE 1. Attachment — viral surface protein binds specific host receptor (explains tissue/species tropism — e.g. HIV needs CD4 + CCR5/CXCR4) 2. Penetration — membrane fusion (enveloped) or receptor-mediated endocytosis 3. Uncoating — capsid removed, genome exposed 4. Biosynthesis — transcription + genome replication + protein synthesis (mechanism is class-specific — this is the "mechanism of replication of the seven virus families" your lecturer flagged) 5. Assembly — capsid proteins package new genomes 6. Release — budding (enveloped, cell can survive and keep shedding virus — chronic infection) vs lysis (non-enveloped, cell dies — acute infection) F. LYTIC, LYSOGENY, LATENCY, PERSISTENCE Lytic cycle: immediate replication → cell lysis → progeny released Lysogenic cycle: genome integrates into host genome (prophage in bacteria; provirus in eukaryotic cells e.g. HIV); dormant, replicates passively with host cell division; can be induced to switch to lytic Latent infection: virus genome persists silently (often in neurons/lymphocytes) with no virion production, can reactivate — HSV, VZV, EBV, CMV Persistent/chronic infection: continuous low-level virion production without killing the cell — Hepatitis B, Hepatitis C Effect of lysogeny on host cell: can confer new properties (lysogenic conversion — e.g. toxin genes in bacteriophage-infected bacteria), or in eukaryotic latency, can predispose to malignant transformation later (EBV, HHV8) G. PATHOGENESIS & HOST DEFENSE Mechanisms of cell damage: direct cytopathic effect (CPE), immune-mediated damage (your own CTLs/inflammation cause the pathology — e.g. Hep B liver damage is mostly immune-mediated, not direct viral killing), cell transformation (oncogenic viruses push cells toward malignancy instead of killing them) Innate defenses: interferons (α/β — block replication in neighbouring uninfected cells by activating antiviral enzyme