HERPES VIRUS – CYTOMEGALOVIRUSES

Cytomegalovirus (CMV) – human herpesvirus‑5 (HHV‑5) – common DNA virus infecting all ages
CMV is transmitted by saliva, urine, genital secretions, breast‑milk, blood, organ transplants, and vertically (placenta)
Human CMV (HCMV) is the clinically important type; murine CMV (MCMV) and rat CMV are used in research

Morphology

Enveloped virus with a lipid bilayer derived from host cell membrane
Icosahedral capsid, 150–200 nm in diameter, containing linear double‑stranded DNA (≈235 kb)
Tegument layer packed with phosphoproteins (major for immune evasion)

Pathogenesis (step‑wise)

Virus enters through mucosal surfaces or broken skin →
Binds to heparan‑sulfate proteoglycans, then specific entry receptors on epithelial, endothelial cells and monocytes →
Fusion of envelope with cell membrane releases capsid into cytoplasm →
Capsid transports to nucleus, DNA injected into nucleus →
Immediate‑early (IE) genes expressed → modulate host immunity, prevent apoptosis →
Early genes → DNA replication, synthesis of viral enzymes →
Late genes → structural proteins, assembly of nucleocapsids →
Nucleocapsids acquire tegument, bud through nuclear membrane → acquire envelope in Golgi/ER →
Cell lysis or exocytosis releases mature virions → spreads to distant organs or remains latent in monocytes/macrophages

Clinical features

Congenital CMV (most common congenital infection)

Immunocompetent (usually self‑limited)

Mononucleosis‑like syndrome: fever, malaise, sore throat, lymphadenopathy, atypical lymphocytes
Mild hepatitis, transient hepatitis‑like transaminase rise

Immunocompromised (HIV, transplant, chemotherapy)

Pneumonitis: non‑productive cough, dyspnea, diffuse interstitial infiltrates
Gastroenteritis/colitis: abdominal pain, watery diarrhea, ulceration of colon
Retinitis: floaters, visual loss, “pizza‑pie” retina, leading to blindness if untreated
Encephalitis/meningoencephalitis: altered sensorium, seizures, focal deficits
Hepatitis, nephritis, myocarditis, bone‑marrow suppression

Complications

Permanent sensorineural hearing loss in newborns
Vision loss from CMV retinitis
Graft rejection or failure in transplant recipients (direct cytopathic effect + immune activation)
Increased susceptibility to opportunistic infections in AIDS patients

Laboratory diagnosis

Direct detection

Viral culture (shell‑vial) from urine, saliva, blood, broncho‑alveolar lavage – rapid cytopathic effect in fibroblasts
Antigenemia assay (pp65 antigen in leukocytes) – useful for monitoring transplant patients

Serology

IgM anti‑CMV → recent infection (appears 1–2 weeks, persists 4–6 weeks)
IgG anti‑CMV → past exposure; rising titre (four‑fold) indicates recent infection

Molecular tests (most sensitive)

PCR for CMV DNA in plasma, urine, CSF, amniotic fluid – quantitative PCR guides therapy in immunocompromised
Real‑time PCR (viral load) – threshold >1000 copies/mL often triggers treatment in transplant setting

Histopathology (when tissue obtained)

Large cells with intranuclear “owl’s‑eye” inclusion bodies (basophilic) surrounded by clear halo

Management (exam‑relevant)

Ganciclovir 5 mg/kg IV q12h (first‑line for severe disease)
Valganciclovir oral pro‑drug (same bio‑equivalent dose) – for congenital infection and maintenance therapy
Foscarnet or Cidofovir for ganciclovir‑resistant strains
Supportive care: transfusions for cytopenias, oxygen for pneumonitis, retinal laser for CMV retinitis
Preventive strategies: CMV‑negative donor to CMV‑negative recipient, prophylactic valganciclovir in high‑risk transplant patients

Memory trick for life‑cycle steps (IE‑E‑L)
“Infect Enter Launch” → Immediate‑early → Early → Late gene phases

Word cue for types: “Humans Make Rats” → Human, Murine, Rat CMV

Key exam points (Robbins, Harsh Mohan, Ananthanarayan, Chatterjee, NCH)