HPV, Polyoma, Adeno, Parvo & Poxviruses

Human papillomavirus

Biology. HPV is a naked (nonenveloped) virus with a circular double-stranded DNA genome. It enters basal cells of squamous epithelium through microabrasions. Cutaneous types cause common and plantar warts; the mucosal types split into low-risk and high-risk groups.

Oncogenesis. In high-risk infection, integration of viral DNA disrupts E2, the viral repressor of the early genes, so the E6 and E7 oncoproteins are overexpressed. E6 tags p53 for ubiquitin-mediated degradation, removing G1 arrest and apoptosis after DNA damage. E7 binds Rb, releasing E2F transcription factors that push the cell into S phase. Loss of Rb feedback causes p16 overexpression, which is used as a surrogate marker of HPV-driven tumors.

Histology and cancer sites. Koilocytes — squamous cells with enlarged, wrinkled, raisin-like hyperchromatic nuclei and a clear perinuclear halo — are the HPV cytopathic effect on Pap smears and biopsies. Cancers arise where squamous and glandular epithelium meet: the cervical squamocolumnar junction (transformation zone), the anal canal (especially in HIV and in men who have sex with men), and the tonsils and base of tongue, where HPV-positive, p16-positive squamous cell carcinoma carries a better prognosis.

Condylomata acuminata (HPV) are cauliflower-like; condylomata lata of secondary syphilis are flat, moist, and teeming with spirochetes.

Vaccine. The 9-valent vaccine covers types 6, 11, 16, 18, 31, 33, 45, 52, and 58. It contains recombinant L1 capsid protein that self-assembles into empty, noninfectious virus-like particles, inducing neutralizing antibodies. It is routine at 11–12 years (it can start at 9), with catch-up through age 26: two doses if started before the 15th birthday, three if started later or if immunocompromised. Vaccination does not replace screening, because not every oncogenic type is covered.

Polyomaviruses

Shared features. Polyomaviruses are naked, circular dsDNA viruses that reactivate when T-cell immunity fails; their oncoprotein, large T antigen, binds Rb much like HPV E7.

JC virus and PML. JC virus lies latent in the kidney and lymphoid tissue. With profound cellular immunosuppression — AIDS, natalizumab (which blocks α4-integrin-mediated immune surveillance of the CNS), or rituximab — it reactivates and lyses oligodendrocytes, causing progressive multifocal leukoencephalopathy. Patients develop subacute, progressive focal deficits such as weakness, visual field loss, aphasia, and cognitive decline. MRI shows multifocal white-matter lesions that do not enhance and exert no mass effect, unlike toxoplasmosis. Histology shows oligodendrocytes with enlarged, ground-glass nuclei and bizarre reactive astrocytes. CSF JC PCR confirms the diagnosis. There is no specific antiviral; treatment restores immunity (antiretroviral therapy, stopping natalizumab).

BK virus. Latent in the urinary tract, BK reactivates under transplant immunosuppression. In kidney recipients it causes BK nephropathy — tubulointerstitial nephritis with rising creatinine and possible graft loss; after hematopoietic stem cell transplant it causes hemorrhagic cystitis. Urine cytology shows virus-laden "decoy cells." The mainstay of treatment is reducing immunosuppression.

Merkel cell polyomavirus. It drives most Merkel cell carcinomas, aggressive neuroendocrine skin cancers of older, sun-damaged, or immunosuppressed patients.

Adenovirus

Biology. Adenovirus is a naked, linear dsDNA virus. Lacking an envelope, it resists many disinfectants; it spreads by droplets, fomites, the fecal-oral route, and poorly chlorinated pools.

• Pharyngoconjunctival fever — fever, pharyngitis, and conjunctivitis in outbreaks among swimmers and campers.
• Epidemic keratoconjunctivitis — highly contagious, spread through eye clinics by hands and instruments; preauricular lymphadenopathy is typical.
• Respiratory disease in military recruits — acute respiratory disease and pneumonia in crowded barracks, prevented by an oral live vaccine against types 4 and 7.
• Acute hemorrhagic cystitis — in children and in transplant recipients.
• Infant gastroenteritis — enteric types 40 and 41.

Severe or disseminated infection in immunocompromised patients is treated with cidofovir, which is nephrotoxic and is given with probenecid and saline hydration.

Parvovirus B19

Biology. The smallest DNA virus: naked, with single-stranded DNA, and able to replicate only in dividing cells. It binds the P antigen (globoside) on erythroid progenitors and lyses them, halting red cell production for about a week (reticulocytopenia). People who lack P antigen are resistant. Other viruses use different receptors — CD21 for EBV, ICAM-1 for rhinovirus, sialic acid for influenza.

Erythema infectiosum (fifth disease). School-age children have a mild prodrome during viremia — the contagious phase — then bright red "slapped" cheeks, then a lacy, reticular rash on the trunk and limbs that fades and can recur with heat, sunlight, or exercise. Because the rash is immune-complex mediated, a child is no longer contagious once it appears and may stay in school.

Fetal infection. Transplacental infection destroys fetal red cell precursors and can cause myocarditis, leading to high-output heart failure and hydrops. Affected fetuses are followed with middle cerebral artery Doppler, and severe anemia is treated with intrauterine transfusion.

Poxviruses

Biology. Poxviruses are the largest human DNA viruses: brick-shaped, enveloped, with linear dsDNA. Uniquely among DNA viruses they replicate entirely in the cytoplasm, so they package their own DNA-dependent RNA polymerase and replication enzymes. Orthopoxviruses include variola (smallpox), vaccinia (the vaccine strain), and mpox.

Molluscum contagiosum. Small, firm, pearly, dome-shaped papules with a central umbilication, spread by skin contact in children and sexually in adults. Biopsy shows large eosinophilic intracytoplasmic molluscum (Henderson-Patterson) bodies. Widespread or giant facial lesions suggest HIV. Lesions resolve over months; curettage or cryotherapy speeds clearance.

Smallpox. Variola was eradicated by vaccination (declared 1980). Its deep, firm pustules develop in synchrony and concentrate on the face and extremities, including palms and soles.

Mpox. A zoonotic orthopoxvirus that spread globally in 2022 through close and sexual contact. Fever and prominent lymphadenopathy — the feature that separates it from smallpox — accompany umbilicated vesiculopustules, often anogenital. Prevention is the 2-dose non-replicating JYNNEOS vaccine; tecovirimat is reserved for severe disease or high-risk patients.