Virus Study Guide

📖 Core Concepts Virus – a sub‑microscopic infectious particle (virion) that can only replicate inside a host cell. Virion components – genome (DNA or RNA), protein capsid (made of capsomeres), and sometimes a host‑derived lipid envelope with glycoproteins. Genome diversity – DNA or RNA, single‑ or double‑stranded, linear or circular, segmented or unsegmented; a virus never has both DNA and RNA. Replication strategy – six‑step viral life cycle: attachment → entry → uncoating → genome replication & gene expression → assembly → release (lysis, budding, or lysogeny). Baltimore classification – groups viruses into 7 classes based on how they generate mRNA (e.g., Class IV = (+)‑sense ssRNA). Antigenic drift vs. shift – drift = gradual point mutations; shift = reassortment of segmented genomes producing a novel strain. Lysogenic vs. lytic – lysogenic: viral genome integrates (provirus/prophage) and replicates with host; lytic: rapid replication → cell rupture. Immune protection – innate sensing (RIG‑I, cGAS) → interferon → adaptive antibodies (IgM → acute, IgG → memory) + cytotoxic T cells. Vaccines & antivirals – vaccines prime immunity without disease; antivirals target entry, polymerase (nucleoside analogues), protease, or host factors. --- 📌 Must Remember Virion size: 20–300 nm (≈ 1/100 the size of a typical bacterium). RNA virus mutation rates: 10⁻³ – 10⁻⁵ substitutions/nt/replication; DNA viruses: 10⁻⁶ – 10⁻⁸. Positive‑sense RNA can be directly translated; negative‑sense RNA must be transcribed to (+)RNA first. Retroviruses: RNA → reverse‑transcribed → integrated DNA (provirus). Key Baltimore classes: dsDNA → mRNA (e.g., Adenovirus) ssDNA (+) → mRNA (Parvovirus) dsRNA → mRNA (Reovirus) (+) ssRNA → mRNA (Coronavirus) (–) ssRNA → mRNA (Influenza) ssRNA‑RT → DNA → mRNA (Retrovirus) dsDNA‑RT → RNA → DNA (Hepadnavirus). Antigenic drift = point mutations → vaccine updates (e.g., seasonal flu). Antigenic shift = reassortment of segmented genomes → pandemic potential (e.g., 2009 H1N1). IgM = acute infection marker; IgG = past infection / immunity marker. Live‑attenuated vaccines → strong immunity but unsafe in immunocompromised; subunit vaccines → safe, protein‑only. --- 🔄 Key Processes Attachment – capsid/glycoprotein binds a specific host receptor (determines host range). Entry – endocytosis or membrane fusion (enveloped) delivers virion inside. Uncoating – capsid removal → genome released in cytoplasm or nucleus. Genome replication & transcription (+)ssRNA → directly translated → RdRp made → replicates genome. (–)ssRNA → RdRp packaged → transcribes (+)mRNA. DNA viruses → use host or viral polymerases (nuclear or cytoplasmic). Retroviruses → reverse transcription → integration. Assembly – capsid proteins self‑assemble around newly made genomes. Release – Lysis (non‑enveloped) → cell rupture. Budding (enveloped) → acquire lipid envelope with glycoproteins. Lysogeny → genome stays integrated, later induced to lytic. --- 🔍 Key Comparisons Positive‑sense RNA vs. Negative‑sense RNA (+)RNA: can act as mRNA → immediate translation. (–)RNA: must first be transcribed to (+)RNA by virion‑carried RdRp. Enveloped vs. Non‑enveloped Viruses Enveloped: acquire lipid membrane → more sensitive to detergents, heat, desiccation; entry via membrane fusion. Non‑enveloped: stable in the environment; entry via endocytosis and capsid penetration. Lytic vs. Lysogenic Cycle Lytic: rapid replication, cell death, high virion output. Lysogenic: genome integrates, replicates silently with host, can be induced. Live‑attenuated vs. Subunit Vaccines Live‑attenuated: mimic natural infection → strong cellular & humoral response; contraindicated in immunocompromised. Subunit: only specific proteins → safer, weaker cellular immunity. --- ⚠️ Common Misunderstandings “Viruses are alive” – they lack metabolism and cellular structure; they are organisms at the edge of life. “All RNA viruses mutate rapidly” – coronaviruses have proofreading enzymes, lowering their rate. “Antigenic drift is the same as shift” – drift = small changes; shift = wholesale genome reassortment. “All vaccines contain live virus” – only live‑attenuated vaccines do; inactivated, subunit, mRNA, and viral‑vector vaccines do not. “IgG means you are currently sick” – IgG indicates past exposure or vaccination, not active infection. --- 🧠 Mental Models / Intuition “Key‑lock” model for entry – viral surface spikes = key; host receptor = lock. Specificity = host range. “Factory line” model for replication – attachment → entry → uncoating = raw material delivery; genome replication = assembly line; release = shipping. “Quasispecies cloud” – imagine a swarm of similar viruses; the cloud’s shape shifts under immune pressure or drugs, explaining rapid adaptation. --- 🚩 Exceptions & Edge Cases Retroviral integration – only retroviruses (Class VI) and Hepadnaviruses (Class VII) integrate DNA into host genome. Proofreading RdRp – coronaviruses possess exonuclease activity, reducing mutation rate compared to most RNA viruses. Ambisense genomes – transcription occurs from both strands after a double‑stranded intermediate (e.g., arenaviruses). Segmented genomes – only viruses with segmented RNA (influenza, rotavirus) can undergo reassortment (antigenic shift). --- 📍 When to Use Which Diagnosing acute infection – test for IgM (early) vs. IgG (past). Choosing antiviral class – if virus uses a polymerase without proofreading → nucleoside analogues are effective; if protease needed for maturation → protease inhibitor. Vaccine strategy for immunocompromised – use subunit or inactivated vaccines, avoid live‑attenuated. Public‑health control – high‑density settings → focus on vaccination + isolation; water‑borne outbreaks → sanitation + oral vaccines. --- 👀 Patterns to Recognize Segmented genome + sudden emergence of a novel strain → suspect antigenic shift (pandemic risk). Rapid point‑mutation accumulation in surface glycoproteins → antigenic drift (seasonal vaccine update). Presence of envelope glycoprotein spikes in EM images → likely enveloped virus, predicts sensitivity to detergents. High mutation rate + RNA genome → expect quasispecies and potential drug resistance. --- 🗂️ Exam Traps “All RNA viruses have high mutation rates” – overlook coronaviruses’ proofreading. “IgM always appears before IgG” – some infections show simultaneous or delayed IgM; timing varies. “Lysogenic cycle always leads to disease” – many prophages are silent; disease only when induced. “All viruses with a lipid envelope are fragile” – some enveloped viruses (e.g., poxviruses) are relatively stable. “Antigenic drift = new virus” – drift changes antigenicity but does not create a new species; shift does. ---