RNA Viruses
A high-yield STEP 1 walkthrough of the RNA viruses, organized by the classification rules boards test (sense, segmentation, naked vs. enveloped, RdRp) and then by clinical system, with buzzword vignettes, classic mnemonics, and comparison tables covering families and the RNA hepatitis viruses.
RNA Viruses: The Classification Framework
RNA viruses are a boards favorite because a few structural rules predict pathogenesis. First classify by genome sense. Positive-sense (+)ssRNA acts directly as mRNA and is immediately translated on host ribosomes, so its purified naked genome is infectious — the key exception is retroviruses, which are (+)ssRNA but must first be reverse-transcribed by virion reverse transcriptase, so naked retroviral RNA is not infectious. Negative-sense (−)ssRNA must carry its own RNA-dependent RNA polymerase (RdRp) inside the virion to make mRNA first — a naked (−) genome is not infectious. dsRNA viruses (Reoviridae) also package an RdRp.
Nearly all RNA viruses replicate in the cytoplasm; the classic exceptions that use the nucleus are influenza (orthomyxovirus) and retroviruses. All RNA viruses are haploid except retroviruses, which are diploid (two identical +ssRNA copies). Because RdRp lacks proofreading, RNA viruses mutate rapidly — the basis of antigenic variation (influenza), quasispecies diversity (HIV, HCV), and the difficulty of vaccine design.
- Positive-sense (+)ssRNA families: Retrovirus, Togavirus, Flavivirus, Coronavirus, Hepevirus, Calicivirus, Picornavirus. Genome acts as mRNA → naked genome is infectious — exception: Retrovirus needs its packaged reverse transcriptase first, so its naked RNA is not infectious.
- Negative-sense (−)ssRNA carry RdRp in the virion — "Always Bring Polymerase Or Fail Replication": Arenavirus, Bunyavirus, Paramyxovirus, Orthomyxovirus, Filovirus, Rhabdovirus. (Deltavirus/HDV is also (−) sense but is defective and uses host RNA polymerase II — it does not package its own RdRp.)
- Naked (non-enveloped) RNA viruses — acid/detergent-stable, survive the gut → fecal-oral spread: Calicivirus, Picornavirus, Reovirus, Hepevirus ("naked CPR & Hep-E"). All other RNA viruses are enveloped.
- Segmented genomes → reassortment (antigenic SHIFT): Bunya, Ortho, Arena, Reo ("BOAR"). Influenza's 8 segments enable pandemics.
- dsRNA = Reoviridae only (Rotavirus, Colorado tick fever); double capsid.
- Replication is cytoplasmic EXCEPT influenza and retroviruses (nuclear).
- The only DNA hepatitis virus is HBV — HAV, HCV, HDV, HEV are all RNA.
RNA Virus Families at a Glance
| Family | Genome / structure | Key feature / buzzword | Major disease(s) | Treatment / vaccine |
|---|---|---|---|---|
| Picornavirus | (+)ssRNA, naked, icosahedral | Smallest RNA; PERCH; rhino acid-labile | Polio, aseptic meningitis, cold, HFMD, myocarditis, hepatitis A | Supportive; polio & HAV vaccines |
| Calicivirus | (+)ssRNA, naked | Norovirus; cruise-ship outbreaks | Viral gastroenteritis | Oral rehydration |
| Reovirus | dsRNA, naked, double capsid | Rotavirus "wheel"; segmented | Infantile watery diarrhea; Colorado tick fever | Oral rehydration; live rotavirus vaccine |
| Flavivirus | (+)ssRNA, enveloped | Arbovirus (Aedes/Culex) | Yellow fever, dengue, Zika, West Nile, hepatitis C | Supportive; YF vaccine; HCV → DAAs (curative) |
| Togavirus | (+)ssRNA, enveloped | Rubella; equine encephalitis | Rubella / congenital rubella | MMR vaccine |
| Retrovirus | (+)ssRNA diploid, reverse transcriptase | Integrates as provirus (nucleus) | HIV/AIDS; HTLV → adult T-cell leukemia | HAART; no cure/vaccine |
| Coronavirus | (+)ssRNA, enveloped, helical | Club-shaped "corona" spikes | Cold, SARS, MERS, COVID-19 | Supportive; vaccines |
| Orthomyxovirus | (−)ssRNA, segmented (8), enveloped | HA + NA; drift vs shift | Influenza | Oseltamivir/zanamivir; vaccines |
| Paramyxovirus | (−)ssRNA, nonsegmented, enveloped | F protein → syncytia | Croup, RSV, measles, mumps | Supportive; palivizumab; MMR |
| Rhabdovirus | (−)ssRNA, bullet-shaped | Negri bodies | Rabies | Post-exposure Ig + vaccine |
| Filovirus | (−)ssRNA, filamentous | Hemorrhagic fever | Ebola, Marburg | Supportive; Ebola vaccine/mAbs |
| Bunyavirus | (−)ssRNA, segmented (3) | Arbovirus / rodent | Hantavirus, California encephalitis, Rift Valley | Supportive |
| Arenavirus | (−)ssRNA, segmented | Rodent; "sandy" host ribosomes | LCMV, Lassa fever | Supportive; ribavirin (Lassa) |
| Deltavirus | (−)ssRNA, defective | Requires HBsAg coat | Hepatitis D | HBV vaccine prevents |
- Picornaviruses = PERCH: Poliovirus, Echovirus, Rhinovirus, Coxsackievirus, Hepatitis A (Hepatovirus). Smallest RNA viruses, naked (+)ssRNA.
- Rhinovirus: >100 serotypes, acid-labile (killed by stomach acid → no GI disease), replicates best at 33 °C (nose) → common cold.
- Poliovirus: fecal-oral → destroys anterior horn motor neurons → asymmetric LMN flaccid paralysis. Salk IPV (killed) vs Sabin OPV (live; mucosal IgA but rare vaccine-associated paralysis).
- Coxsackie A → hand-foot-mouth disease, herpangina (oral vesicles/ulcers), aseptic meningitis. Coxsackie B → myocarditis/pericarditis, dilated cardiomyopathy, pleurodynia (Bornholm/"devil's grip"). B = Body/heart.
- Rotavirus (reovirus, dsRNA): #1 cause of severe childhood diarrhea; NSP4 enterotoxin + villous destruction → watery diarrhea; winter peaks; live oral vaccine.
- Norovirus (calicivirus): most common cause of nonbacterial gastroenteritis outbreaks — cruise ships, schools; explosive vomiting/diarrhea, self-limited.
Respiratory RNA Viruses: Influenza & Paramyxoviruses
Two enveloped families dominate respiratory questions. Orthomyxovirus (influenza) has a segmented, 8-piece (−)ssRNA genome and two surface glycoproteins: hemagglutinin (HA) binds host sialic acid for entry, and neuraminidase (NA) cleaves sialic acid to release progeny virions. Small point mutations in HA/NA cause antigenic drift (annual epidemics); reassortment of whole segments between human and animal strains causes antigenic shift — the abrupt, pandemic-causing change (e.g., H1N1). NA inhibitors oseltamivir/zanamivir treat and prevent it, and giving aspirin to a febrile child risks Reye syndrome (hepatoencephalopathy).
Paramyxoviruses are nonsegmented (−)ssRNA and all carry an F (fusion) protein that fuses infected cells into multinucleated giant cells (syncytia). Parainfluenza → croup (barking/seal-bark cough, inspiratory stridor, steeple sign on neck X-ray). RSV → bronchiolitis and pneumonia in infants; prevent in high-risk premature infants with palivizumab (anti-F monoclonal antibody).
- Measles (rubeola, paramyxovirus): 3 C's — Cough, Coryza, Conjunctivitis + Koplik spots (pathognomonic blue-white buccal spots) → cephalocaudal maculopapular rash. Complications: giant-cell pneumonia (top killer), encephalitis, SSPE (years later). Vitamin A reduces mortality; MMR prevents.
- Mumps (paramyxovirus): parotitis, orchitis (post-pubertal; rare infertility), aseptic meningitis, pancreatitis.
- Rabies (rhabdovirus, bullet-shaped): Negri bodies (cytoplasmic inclusions in hippocampal/Purkinje neurons); travels retrograde up axons to CNS; long incubation → hydrophobia, agitation, then paralysis/coma. Post-exposure prophylaxis = wound care + rabies Ig (passive) + inactivated vaccine (active).
- Flavivirus arboviruses (Aedes): Yellow fever (jaundice, black vomit, Councilman bodies; live vaccine); Dengue ("breakbone fever"; hemorrhagic fever on 2nd infection via antibody-dependent enhancement); Zika (congenital microcephaly; sexual transmission). West Nile (Culex) → encephalitis.
- Rubella (togavirus): postauricular lymphadenopathy + head-to-toe rash; congenital rubella = PDA + cataracts + deafness ("blueberry muffin" baby).
- Hemorrhagic fevers: Ebola/Marburg (filovirus); Hantavirus (bunyavirus; deer mouse; pulmonary syndrome); Lassa (arenavirus; ribavirin).
- "Toddler with a barking/seal-like cough, inspiratory stridor, and steeple sign on neck X-ray" → Parainfluenza (croup) → humidified air, corticosteroids ± nebulized epinephrine.
- "Blue-white spots on the buccal mucosa before a rash spreading from the hairline downward; unvaccinated child" → Measles (rubeola) → supportive + vitamin A.
- "Hydrophobia, hypersalivation, and agitation weeks after a bat exposure; cytoplasmic Negri bodies at autopsy" → Rabies → fatal once symptomatic; prevent with post-exposure Ig + vaccine.
- "Wheezing infant in winter with apnea and bronchiolitis" → RSV → supportive O₂/fluids; palivizumab prophylaxis in high-risk preemies.
- "Traveler with high fever, severe retro-orbital and joint 'breakbone' pain, then thrombocytopenia/bleeding on a second trip" → Dengue → supportive; avoid NSAIDs.
- "Fever, jaundice, and black (bloody) vomit after jungle travel; Councilman bodies in the liver" → Yellow fever → supportive; live-attenuated vaccine prevents.
- "Explosive vomiting and watery diarrhea sweeping a cruise ship" → Norovirus → oral rehydration; self-limited.
- PERCH — Picornaviruses: Polio, Echo, Rhino, Coxsackie, Hepatitis A.
- "Naked CPR & Hep-E" — non-enveloped RNA viruses: Calici, Picorna, Reo, Hep E.
- BOAR — segmented (reassorting) RNA viruses: Bunya, Ortho, Arena, Reo.
- 3 C's of measles — Cough, Coryza, Conjunctivitis (+ Koplik spots).
- Congenital rubella triad — PDA, Cataracts, Deafness.
- "Drift = small/seasonal; Shift = big/pandemic" — influenza antigenic variation.
- Coxsackie B = Body (heart) myocarditis/pericarditis; Coxsackie A → mouth & skin (HFMD, herpangina).
RNA Hepatitis Viruses (HBV is the DNA exception)
| Virus | Family | Transmission | Chronic? | High-yield clue |
|---|---|---|---|---|
| HAV | Picornavirus | Fecal-oral (shellfish, travel) | No | Acute, self-limited; vaccine available |
| HCV | Flavivirus | Blood/IVDU, sexual | Yes (majority) | Cirrhosis, HCC; DAAs curative; no vaccine |
| HDV | Deltavirus | Blood/sexual | Depends | Defective — needs HBsAg; superinfection worse than coinfection |
| HEV | Hepevirus | Fecal-oral (waterborne) | No (chronic if immunosuppressed) | Fulminant in pregnancy (high mortality) |
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