RNA viruses outnumber DNA viruses and cause most acute viral illness — the common cold, influenza, measles, gastroenteritis, and HIV. Step 1 sorts them by genome polarity, envelope, and segmentation, then asks for the disease, the vaccine, or the replication quirk. Polarity is the organizing idea: it decides whether the genome can be read immediately or must first be copied.
Evidence-based · For exam prep, not medical advice
update Updated October 2026
Date of last content change
Built by surgery and anesthesiology residents
Written for USMLE Step 1 · Free to read
bolt The 60-second version
RNA viruses outnumber DNA viruses and cause most acute viral illness — the common cold, influenza, measles, gastroenteritis, and HIV. Step 1 sorts them by genome polarity, envelope, and segmentation, then asks for the disease, the vaccine, or the replication quirk.
check_circlePositive-sense RNA acts directly as mRNA and is infectious when purified; negative-sense RNA needs a virion RNA-dependent RNA polymerase.
check_circleAll RNA viruses replicate in the cytoplasm except influenza and retroviruses.
check_circleAll RNA viruses are single-stranded except reoviruses (rotavirus), which are double-stranded.
check_circleSegmented genomes (BOARding flight: Bunya, Orthomyxo, Arena, Reo) allow reassortment — the basis of influenza antigenic shift.
check_circleNaked RNA viruses: picornavirus, calicivirus (norovirus), reovirus, and hepevirus.
check_circleRetroviruses (HIV) carry reverse transcriptase and integrate into the host genome.
target What you'll be able to do · aligned to USMLE Step 1 · Microbiology — Virology
MICRODistinguish positive-sense, negative-sense, and double-stranded RNA viruses and explain the consequences for replication.
MICROClassify the major RNA virus families by envelope, polarity, and segmentation.
MICROContrast antigenic drift and shift in influenza.
PHARMMap antiretroviral drug classes onto the HIV replication cycle.
How RNA viruses are tested on Step 1
Vignettes describe a syndrome (cough, coryza, conjunctivitis, and Koplik spots; watery diarrhea in a daycare; flaccid paralysis) and ask for the family, polarity, or vaccine type.
workspace_premium Polarity in one sentence
Positive sense = the genome is mRNA and ribosomes translate it on arrival. Negative sense = the genome is the complement of mRNA, so the virus must bring its own polymerase to make mRNA.
Positive vs negative sense
Genome polarity determines the first step after entry.
Polarity. Retroviruses are positive-sense but do not use their genome as mRNA directly; they reverse-transcribe it into DNA first.
Family
Structure
Key viruses and diseases
Picornaviridae
+ss, naked
Poliovirus, echovirus, rhinovirus, coxsackie (hand-foot-mouth, myocarditis), hepatitis A
Caliciviridae
+ss, naked
Norovirus — cruise-ship gastroenteritis
Reoviridae
dsRNA, segmented, naked
Rotavirus — severe diarrhea in infants; live oral vaccine
Measles, mumps, parainfluenza (croup); RSV (bronchiolitis) is now classified in the closely related Pneumoviridae
Rhabdoviridae
−ss, enveloped, bullet-shaped
Rabies — Negri bodies
Filoviridae
−ss, enveloped
Ebola, Marburg — hemorrhagic fever
Picornaviruses (PERCH: Polio, Echo, Rhino, Coxsackie, HAV) translate one large polypeptide that is cleaved by viral proteases.
Influenza: drift and shift
Influenza changes its surface proteins, hemagglutinin (attachment) and neuraminidase (release), in two ways.
Drift vs shift. Neuraminidase inhibitors (oseltamivir, zanamivir) block virion release; baloxavir inhibits the cap-dependent endonuclease.
Retroviruses and HIV
HIV is a diploid positive-sense RNA virus. Its replication cycle is the map for antiretroviral drug classes.
HIV life cycle. Homozygous CCR5 deletion confers resistance to R5-tropic strains.
functions Worked example — choose the vaccine type
A 4-month-old receives an oral vaccine against the most common cause of severe infant diarrhea worldwide. What type of virus is targeted, and what is unusual about its genome?
Rotavirus is the leading cause of severe dehydrating diarrhea in infants.
It belongs to the Reoviridae, the only double-stranded RNA viruses.
Its genome is segmented, so reassortant strains can be engineered for vaccines.
The oral live vaccine carries a small risk of intussusception.
Answer. Rotavirus — a naked, segmented, double-stranded RNA virus (Reoviridae). The vaccine is live attenuated and oral.
Hepatitis viruses compared
Five unrelated viruses share the name hepatitis. Four are RNA viruses; hepatitis B is the DNA exception.
Virus
Family and genome
Transmission
Chronic?
Key point
HAV
Picornavirus, +ssRNA
Fecal-oral
No
Travel, shellfish; vaccine available
HBV
Hepadnavirus, partial dsDNA
Parenteral, sexual, perinatal
Yes (90% of neonates, < 5% of adults)
Reverse transcriptase; HCC risk
HCV
Flavivirus, +ssRNA
Blood (IV drug use)
Yes (most)
No vaccine; cured by direct-acting antivirals
HDV
Deltavirus, −ssRNA (circular)
Parenteral
Yes, with HBV
Needs HBsAg to make its envelope
HEV
Hepevirus, +ssRNA
Fecal-oral (water)
Rarely
Fulminant hepatitis in pregnancy
Mnemonic: the vowels (A and E) are fecal-oral — they go through the bowels.
1. An unvaccinated child has fever, cough, coryza, conjunctivitis, and white spots on the buccal mucosa, followed by a maculopapular rash spreading from the head down. Which family causes this?
Explanation. Measles is a paramyxovirus; Koplik spots precede the cephalocaudal rash.
2. Which virus has a double-stranded RNA genome?
Explanation. Reoviridae, including rotavirus, are the only double-stranded RNA viruses.
3. Purified genomic RNA from which virus would be infectious if injected into a cell?
Explanation. Poliovirus is a positive-sense RNA virus; its genome acts directly as mRNA.
Frequently asked questions
What is the difference between positive-sense and negative-sense RNA viruses?expand_more
Positive-sense RNA can be translated directly by host ribosomes. Negative-sense RNA must first be copied into mRNA by an RNA-dependent RNA polymerase packaged in the virion.
Which RNA viruses are segmented?expand_more
Bunyaviruses, orthomyxoviruses (influenza), arenaviruses, and reoviruses (rotavirus) — remembered as BOARding flight.
Which RNA viruses replicate in the nucleus?expand_more
Influenza (orthomyxovirus) and retroviruses such as HIV. Other RNA viruses replicate in the cytoplasm.
Why does influenza cause pandemics?expand_more
Its segmented genome allows two strains infecting one cell to swap segments (antigenic shift), producing a new hemagglutinin or neuraminidase subtype to which the population has no immunity.
Study smarter with a short weekly email. No spam — unsubscribe anytime.
✓ You're in — talk soon.
Reading is one thing. Remembering is another.
Turn this guide into questions you’ll actually remember
Progress Note turns concepts like this into adaptive questions and spaced review, so difficult topics come back to you exactly when you’re about to forget them.