Essential Medical Virology: Structure, OmpathStudy

MEDICAL VIROLOGY — SECTION 1 (Comprehensive Notes) Introduction to Virology A virus is an obligate intracellular parasite — it has no ribosomes, no independent metabolism, and cannot reproduce outside a living host cell. It hijacks host machinery to replicate. This is why antivirals target specific steps in replication rather than killing the organism outright (unlike antibiotics on bacteria). Structure of a virion : Genome : DNA or RNA (never both), single-stranded (ss) or double-stranded (ds), linear or circular Capsid : protein shell made of capsomeres; protects genome, mediates attachment in non-enveloped viruses Envelope : lipid bilayer derived from host membrane, studded with viral glycoproteins (only some viruses have this) Enveloped vs Non-enveloped — clinical relevance : Enveloped = fragile (destroyed by heat, drying, alcohol, detergents) → spreads by direct contact, droplets, blood (e.g. HIV, influenza, herpesviruses) Non-enveloped = tough, survives acid/drying → spreads faecal-oral, on surfaces (e.g. poliovirus, rotavirus, adenovirus) Capsid symmetry (3 types): Helical – coiled rod shape (influenza, rabies) Icosahedral – 20-sided, most efficient packing (poliovirus, adenovirus, herpesvirus) Complex – irregular, doesn't fit either (poxvirus, bacteriophages) --- 1. Classification — ICTV and Baltimore System ICTV (International Committee on Taxonomy of Viruses) Function: gives every virus one internationally standardized name; sets the rules for viral taxonomy Hierarchy used: Order → Family → Subfamily → Genus → Species Naming based on genome type, structure, replication strategy, host range — NOT on disease caused Baltimore Classification — groups viruses by genome type + how they make mRNA. This determines their whole replication strategy. Class Genome mRNA synthesis Example --- --- --- --- I dsDNA Direct transcription by host RNA pol (or own pol) Herpesvirus, Adenovirus, Poxvirus II ssDNA (+) Converted to dsDNA first, then transcribed Parvovirus III dsRNA Viral RNA-dependent RNA polymerase (RdRp) transcribes mRNA directly from genome Rotavirus (Reovirus) IV (+)ssRNA Genome IS the mRNA — translated directly Poliovirus, Rubella, Hep A, Coronaviruses V (–)ssRNA Must first be transcribed into (+)RNA by viral RdRp before translation Influenza, Rabies, Measles VI ssRNA-RT (Retrovirus) Reverse transcriptase converts RNA → DNA → integrates into host genome → transcribed HIV VII dsDNA-RT dsDNA → transcribed to RNA → reverse transcribed back to DNA Hepatitis B Why this matters for exams : (+)ssRNA viruses can act as their own mRNA immediately (fast replication); (–)ssRNA viruses must carry their own RdRp packaged in the virion (because the cell has no enzyme to read negative-sense RNA); retroviruses are unique in permanently integrating into host DNA, which is why HIV can never be fully cleared. Atypical infectious agents (don't fit normal virus definition): Prions : infectious misfolded proteins, NO nucleic acid at all; cause spongiform encephalopathies (CJD, Kuru, BSE/mad cow); resistant to normal heat sterilization and disinfectants — need special protocols Slow viruses / slow infections : conventional viruses but with very long incubation and progressive course (e.g. measles virus causing SSPE years later) --- 2. Viral Replication Cycle (general steps, all viruses) 1. Attachment – viral surface protein binds specific host receptor (explains tissue tropism, e.g. HIV needs CD4+CCR5) 2. Penetration – entry by fusion (enveloped) or endocytosis 3. Uncoating – capsid removed, genome released into cytoplasm/nucleus 4. Biosynthesis – transcription, genome replication, protein translation (mechanism depends on Baltimore class — see table above) 5. Assembly – new capsids package new genomes 6. Maturation – proteins cleaved/folded into infectious form 7. Release – by cell lysis (non-enveloped, kills cell) or budding (enveloped, cell may survive) One-step growth curve (used to study phage/virus replication kinetics): Adsorption – attachment to host Latent period – no free infectious virus detectable (replication happening inside, hidden) Rise period (burst) – progeny virus released rapidly Burst size – number of new virions released per infected cell Lytic vs Lysogenic cycle (classically taught with bacteriophages, but concept applies to latent viruses generally): Feature Lytic Lysogenic --- --- --- Outcome Host cell destroyed immediately Phage DNA integrates as prophage ; host survives Timing Immediate replication Dormant, can persist for many generations Reactivation N/A Induction (e.g. UV light, stress) → switches to lytic Example T4 phage Lambda phage Effects of lysogeny on the host cell : Immunity to superinfection — lysogenized cell resists infection by the same/similar phage Lysogenic (phage) conversion — host bacterium gains new genetic traits from prophage genes (classic exam example: Corynebacterium diphtheriae only produces diphtheria toxin when carrying the tox gene from a lysogenic phage; same princip