RNA virus Study Guide

📖 Core Concepts RNA virus – a virus whose genetic material is ribonucleic acid (RNA). RNA‑dependent RNA polymerase (RdRp) – enzyme encoded by every RNA virus; copies RNA genomes but lacks proofreading, giving high mutation rates. Genome sense & polarity Positive‑sense (+) ssRNA – functions directly as mRNA; can be translated immediately. Negative‑sense (‑) ssRNA – complementary to mRNA; must be transcribed to (+) RNA by virion‑carried RdRp before translation. Ambisense – genome contains both (+) and (‑) coding regions; part of the genome is transcribed before translation, the other part is used directly. Baltimore classification (relevant groups) Group III – dsRNA viruses. Group IV – (+) ssRNA viruses (polyprotein strategy). Group V – (‑) ssRNA viruses (RdRp packaged in virion). Group VI – Retroviruses (RNA → DNA → integration). Mutation & genetic stability – error‑prone RdRp → high mutation rate, hampering long‑lasting vaccine efficacy. Genetic recombination – exchange of genome segments when two viruses co‑infect a cell; a major driver of new strains (e.g., influenza, coronavirus, HIV). Classification – RNA viruses belong to the realm Riboviria (Baltimore groups III‑VI) and are grouped into 5 orders, 47 families (e.g., Orthomyxoviridae, Coronaviridae). --- 📌 Must Remember +ssRNA = mRNA → immediate translation. ‑ssRNA = needs virion RdRp → transcription → mRNA. Ambisense = mixed strategy (e.g., arenaviruses). RdRp has no 3’→5’ exonuclease → high mutation rate. Retroviral lifecycle: RNA → reverse transcriptase → cDNA → integrase → provirus → host RNA polymerase II transcription. Recombination occurs in Picornaviridae, Retroviridae, Reoviridae, Orthomyxoviridae, Coronaviridae. Key families & diseases: Orthomyxoviridae – influenza (respiratory droplets). Flaviviridae – dengue, West Nile (mosquito vector). Rhabdoviridae – rabies (bite). Coronaviridae – SARS‑CoV‑2 (respiratory droplets). Diagnostic cornerstone: RT‑PCR detects viral RNA; serology detects antibodies. --- 🔄 Key Processes Group IV (+) ssRNA replication Genome enters cytoplasm → direct translation of a single polyprotein. Viral/host proteases cleave polyprotein → functional proteins (including RdRp). RdRp synthesizes a complementary (‑) strand → double‑stranded replicative intermediate. The intermediate serves as template for new (+) genomes and subgenomic mRNAs. Group V (‑) ssRNA replication Virion delivers RdRp into the host cell. RdRp transcribes the (‑) genome into (+) mRNAs. (+) mRNAs are translated → viral proteins (including more RdRp). New RdRp copies (+) mRNAs back to (‑) genomes for packaging. Group VI Retroviral lifecycle Uncoating → reverse transcriptase makes cDNA from RNA. cDNA → integrase inserts double‑stranded DNA into host genome (provirus). Host RNA polymerase II transcribes provirus → viral mRNAs & genomes. Recombination (template switching) During RNA synthesis (RdRp or reverse transcriptase), the polymerase can jump from one template to another → chimeric genomes. --- 🔍 Key Comparisons Positive‑sense (+) ssRNA vs Negative‑sense (‑) ssRNA +ssRNA: directly translational → no polymerase in virion. ‑ssRNA: requires virion RdRp → transcription before translation. Group IV (+) ssRNA vs Group V (‑) ssRNA Group IV: polyprotein → proteolytic processing. Group V: segmented genomes often, no polyprotein. Retrovirus vs Other RNA viruses Retrovirus: RNA → DNA → integration; unique enzymes (reverse transcriptase, integrase). Others: stay in RNA form; replicate in cytoplasm (most) or nucleus (some). Recombination vs Mutation Mutation: point errors during replication. Recombination: wholesale exchange of genome blocks between co‑infecting viruses. --- ⚠️ Common Misunderstandings “All RNA viruses replicate in the cytoplasm.” False: some (e.g., influenza) replicate in the nucleus. “Negative‑sense RNA can be translated directly.” False: needs RdRp‑mediated transcription first. “Retroviruses have low mutation rates because they use a DNA intermediate.” False: reverse transcription is error‑prone; mutations become fixed in both DNA strands. “RdRp proofreading ensures high fidelity.” False: RdRp lacks proofreading, driving high variability. --- 🧠 Mental Models / Intuition “Copy machine without a spell‑checker” – RdRp copies RNA rapidly but never corrects mistakes → high diversity. “Phone book vs recipe” – (+) ssRNA is like a ready‑to‑read phone book (mRNA); (‑) ssRNA is a scrambled recipe that must be rewritten before you can cook (translate). “Plug‑and‑play virus” – Retrovirus brings its own “plug” (reverse transcriptase + integrase) to insert a new “app” (proviral DNA) into the host’s operating system. --- 🚩 Exceptions & Edge Cases Segmentation – Many dsRNA (Reoviridae) and some (-) ssRNA viruses (Orthomyxoviridae) have segmented genomes, allowing reassortment (a form of recombination). Nuclear replication – Influenza (Group V) and some bunyaviruses replicate their RNA in the nucleus, contrary to the usual cytoplasmic rule. Polyprotein processing – Not all (+) ssRNA viruses use a polyprotein (e.g., coronaviruses produce multiple subgenomic RNAs). Ambisense viruses – Arenaviruses and Bunyaviridae have ambisense segments; transcription timing differs for each strand. --- 📍 When to Use Which Diagnostic choice RT‑PCR → when you need rapid, specific detection of viral RNA (most acute infections). Serology → when assessing past exposure or immunity (e.g., post‑vaccination). Vaccine strategy Inactivated/live‑attenuated → feasible for relatively stable viruses (e.g., measles). mRNA or vectored vaccines → preferred for high‑mutation viruses (influenza, SARS‑CoV‑2) to allow rapid redesign. Treatment focus RdRp inhibitors (e.g., remdesivir) → effective against Group IV, V, III viruses. Reverse transcriptase inhibitors → only for retroviruses (HIV, HTLV). Predicting evolution If a virus has a segmented genome, watch for reassortment (e.g., new influenza subtypes). If a virus is highly mutable (no proofreading), expect antigenic drift → frequent vaccine updates. --- 👀 Patterns to Recognize High mutation + envelope proteins → rapid antigenic drift (influenza, HIV). Segmented genome + co‑infection → reassortment → sudden phenotype shift (pandemic flu, rotavirus). Polyprotein → protease cleavage sites → typical of picornaviruses and many coronaviruses. Presence of RdRp gene in the virion → indicates (‑) ssRNA (Group V) or dsRNA (Group III). Reverse‑transcriptase motifs (e.g., YXDD) → hallmark of retroviral genomes. --- 🗂️ Exam Traps “RNA viruses have DNA intermediates.” – Only retroviruses (Group VI) do; all others stay RNA. “Negative‑sense RNA genomes are directly infectious.” – They are not; they require the packaged RdRp. “All RNA viruses are cytoplasmic.” – Influenza and some others replicate in the nucleus. “High mutation rates mean all RNA viruses are unvaccinable.” – Many (e.g., measles, polio) have stable antigens despite being RNA viruses. “Recombination only occurs in retroviruses.” – It also occurs in dsRNA, negative‑sense, and positive‑sense families (e.g., coronaviruses). “RT‑PCR detects DNA viruses.” – It specifically amplifies RNA after reverse transcription; DNA viruses require standard PCR. ---