How DNA viruses are tested on Step 1

Questions give a rash, a cancer, or an anemia and ask for the virus family, its genome, or the structural feature that sets it apart. Exceptions to the general rules are high-yield.

workspace_premium Rules of thumb

DNA viruses are double-stranded, linear, icosahedral, and replicate in the nucleus. Exceptions: parvovirus is single-stranded; papilloma, polyoma, and hepadna are circular; poxvirus is complex and replicates in the cytoplasm.

The seven DNA virus families

Sort the families by envelope first; envelope status predicts stability in the environment and spread by fomites.

DNA viruses (HHAPPPPy)HerpesviridaeEnveloped; HSV,VZV, EBV, CMVHepadnaviridaeEnveloped; HBVPoxviridaeEnveloped;cytoplasmicSmall nakedAdeno,papilloma,polyoma; dsDNAParvoviridaeNaked,single-stranded
DNA virus families. Naked viruses resist drying and detergents, which helps adenovirus spread through swimming pools and fomites.
FamilyGenomeKey virusesClassic disease
Herpesviridaeds, linear; envelopedHSV-1/2, VZV, EBV, CMV, HHV-6/7/8See the herpesvirus guide; latency is the theme
HepadnaviridaePartial ds, circular; envelopedHepatitis B virusAcute and chronic hepatitis, cirrhosis, hepatocellular carcinoma
Adenoviridaeds, linear; nakedAdenovirusPharyngoconjunctival fever, hemorrhagic cystitis, pneumonia, gastroenteritis
Papillomaviridaeds, circular; nakedHPVWarts (1, 2, 6, 11); cervical, anal, and oropharyngeal cancer (16, 18)
Polyomaviridaeds, circular; nakedJC virus, BK virusJC: PML in AIDS; BK: transplant nephropathy
Poxviridaeds, linear; enveloped, largestVariola, vaccinia, molluscum, mpoxSmallpox; molluscum contagiosum (umbilicated papules)
Parvoviridaess, linear; naked, smallestParvovirus B19Erythema infectiosum, aplastic crisis, hydrops fetalis

Parvovirus B19 is both the smallest DNA virus and the only single-stranded one.

Parvovirus B19 and adenovirus

Parvovirus B19 infects erythroid progenitors through the P antigen, briefly halting red cell production.

Healthy childErythema infectiosum (fifth disease)"Slapped cheek" rash, then lacy rash onlimbsMild, self-limitedAdults: symmetric arthritisVulnerable hostSickle cell or spherocytosis → aplasticcrisisImmunocompromised → chronic pure redcell aplasiaPregnancy → hydrops fetalis, fetal deathLow reticulocyte count is the cluevs
Parvovirus B19. A short pause in erythropoiesis is harmless with normal red cell lifespan but catastrophic when red cells survive only days.

Hepatitis B and HPV

Two DNA viruses dominate oncogenesis questions.

PartialdsDNAEntershepatocytenucleuscccDNACovalentlyclosed circlePregenomicRNAHost RNApolymerase IIRT stepViral reversetranscriptasemakes DNANewvirionsHBsAgenvelope
HBV replicates through RNA. Its polymerase is a reverse transcriptase, so nucleoside analogues such as tenofovir and entecavir suppress it; cccDNA persistence explains why cure is rare.
FeatureHPVHBV
Oncogenic mechanismE6 degrades p53; E7 binds and inactivates RbIntegration, chronic inflammation, HBx protein
CancerCervical, anal, penile, oropharyngeal squamous cell carcinomaHepatocellular carcinoma (even without cirrhosis)
Benign lesionsCommon and plantar warts; condyloma acuminatum (6, 11)—
Vaccine9-valent recombinant L1 capsid proteinRecombinant HBsAg

Mnemonic: E6 → p53 (6 is near 5), E7 → Rb.

functions Worked example — explain the anemia

A 7-year-old with sickle cell disease has fatigue and pallor a week after a mild febrile illness with red cheeks. Hemoglobin fell from 8.5 to 4.2 g/dL, and the reticulocyte count is 0.2%. What virus is responsible, and why is the reticulocyte count low?

  1. A sudden hemoglobin drop with absent reticulocytes means red cell production has stopped — aplastic crisis.
  2. Parvovirus B19 infects erythroid progenitors through the P antigen and kills them.
  3. In sickle cell disease, red cells survive only 10–20 days, so a brief halt in production causes severe anemia.

Answer. Parvovirus B19, a single-stranded DNA virus. The reticulocyte count is low because the virus destroys erythroid precursors; treatment is transfusion.

Oncogenic viruses

DNA viruses dominate the list of cancer-causing viruses, but two RNA viruses also belong on it.

VirusGenomeAssociated cancerMechanism
HPV 16, 18DNACervical, anal, penile, oropharyngeal SCCE6 → p53 loss; E7 → Rb loss
HBVDNAHepatocellular carcinomaIntegration, chronic inflammation, HBx
EBVDNABurkitt, Hodgkin, nasopharyngeal carcinoma, PTLDB-cell immortalization; t(8;14) in Burkitt
HHV-8DNAKaposi sarcoma, primary effusion lymphomaViral cyclin and cytokine homologs
Merkel cell polyomavirusDNAMerkel cell carcinomaLarge T antigen inactivates Rb
HCVRNAHepatocellular carcinoma, B-cell lymphomaChronic inflammation and cirrhosis
HTLV-1RNA (retrovirus)Adult T-cell leukemia/lymphomaTax protein activates growth genes

HPV vaccination and HBV vaccination are the two most effective cancer-prevention vaccines.