Module 4 · DNA Viruses
DNA Viruses
DNA viruses replicate with the higher fidelity of DNA polymerases (mutation rates ~10−7/base), can establish long-term latency, and account for some of the most consequential cancers and chronic infections of humans. They mostly replicate in the nucleus (poxviruses excepted) and use the host transcription machinery.
1. Papillomaviruses (HPV)
Small, circular dsDNA, ~8 kb, T = 7 capsid built of L1 + L2. Infect basal keratinocytes through micro-abrasions; replicate in differentiating epithelium. >200 HPV types known; ~12 are oncogenic (notably HPV16, HPV18). HPV is the cause of essentially all cervical cancer, and contributes to anogenital, oropharyngeal, and skin cancers. The oncogenes E6 (degrades p53) and E7 (inactivates Rb) drive cell-cycle entry.
The HPV vaccine (Gardasil 9) is a recombinant L1 virus-like particle — no genome, but assembling into the same T = 7 icosahedron and inducing strong neutralising antibodies. Population-level cervical-cancer incidence has begun to fall in countries with high-coverage vaccination programmes (Australia, UK, Sweden); cervical cancer is poised to become the first vaccine-preventable cancer.
2. Herpesviruses
Large enveloped dsDNA viruses, ~125–240 kb, T = 16 capsid surrounded by a proteinaceous tegument and a lipid envelope. Eight human herpesviruses, all establishing lifelong latency:
- HSV-1, HSV-2 — oral and genital herpes; latent in trigeminal/sacral ganglia.
- VZV — varicella (chickenpox); latent in dorsal root ganglia; reactivates as zoster (shingles). Live and recombinant subunit (Shingrix) vaccines.
- EBV — infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma; latent in B cells. Recently linked causally to multiple sclerosis (Bjornevik 2022).
- CMV — congenital infection (leading non-genetic cause of hearing loss), severe in transplant recipients.
- HHV-6, -7 — roseola; HHV-6 integrates into host telomeres in ~1% of people.
- KSHV (HHV-8) — Kaposi’s sarcoma in AIDS, primary effusion lymphoma.
3. Adenoviruses
Non-enveloped dsDNA, ~36 kb, distinctive icosahedral capsid with antenna-like fibres at each vertex. Cause respiratory infections, conjunctivitis, gastroenteritis. Replication-defective adenoviruses are the basis of several vaccines (ChAdOx1 for AstraZeneca COVID-19, Ad26 for Janssen) and many gene-therapy vectors. Adenoviral E1A and E1B oncoproteins inactivate Rb and p53 respectively — the prototypes for understanding viral oncogenesis.
4. Poxviruses
The largest animal viruses by far — brick-shaped, ~360 nm, ~200 kb genome, hundreds of genes. Unique among DNA viruses for replicating in the cytoplasm; the virion brings its own RNA polymerase. Variola virus caused smallpox — eradicated by 1980 thanks to the live vaccinia vaccine, the first human disease ever eradicated by deliberate intervention. Monkeypox (now mpox) is a related orthopoxvirus that emerged as a global concern in 2022 with sustained human-to-human transmission.
5. Hepatitis B (a Pararetrovirus)
Hepatitis B virus (HBV) is in Baltimore Group VII: dsDNA genome but replicates via an RNA intermediate using viral reverse transcriptase. The result is high mutation rate (despite being “DNA”) and the persistence of cccDNA in the nucleus of infected hepatocytes — a stable archive that current antivirals (entecavir, tenofovir, RT inhibitors borrowed from HIV) suppress but do not eliminate. ~250 million people are chronically infected; HBV is a major cause of hepatocellular carcinoma. The HBV vaccine (recombinant HBsAg) is the first cancer-preventing vaccine in human history.
6. Polyomaviruses
Small, circular dsDNA, T = 7. SV40 was the laboratory workhorse of cancer biology — its large T antigen, an Rb and p53 inhibitor, is the prototype viral oncoprotein. JC virus causes progressive multifocal leukoencephalopathy in the immunosuppressed; BK virus is a problem in renal transplant recipients; Merkel-cell polyomavirus (discovered 2008) causes Merkel-cell carcinoma. Many healthy adults carry these viruses asymptomatically.