VirusesHerpesviridae

Cytomegalovirus

A double-stranded DNA herpesvirus (HHV-5) that causes opportunistic infections in immunocompromised hosts and congenital disease, characterized by cells with large intranuclear "owl-eye" inclusions.

Organism Card

DomainMust know
Identity
  • HHV-5; enveloped dsDNA virus; Herpesviridae (Betaherpesvirinae) [1]
  • Largest human herpesvirus; establishes lifelong latency in myeloid progenitor cells
  • HK seroprevalence > 90% — most blood products CMV +ve [2][3]
  • Reactivation in immunocompromised (T-cell deficiency) is the major clinical concern
Reservoir / transmission
  • Humans only reservoir
  • Transmission: saliva, genital secretions, breastmilk, blood products, organ transplant, transplacental [4]
  • Leukodepleted blood components reduce transfusion-transmitted CMV when CMV-seroneg products unavailable [3]
Key virulence
  • Immune evasion: downregulates MHC-I, encodes IL-10 homologue, Fc receptor decoy
  • Cytopathic effect: characteristic "owl-eye" nuclear inclusions (enlarged cells with intranuclear + cytoplasmic inclusions)
  • Latency in CD34+ myeloid progenitors → reactivation with immunosuppression
Clinical syndromes
  • Immunocompetent: mostly asymptomatic; mononucleosis-like syndrome (heterophile-negative) — less prominent than EBV [4]
  • Immunocompromised (transplant/HIV): retinitis, pneumonitis, colitis/esophagitis, hepatitis, encephalitis, BM failure [4][5]
  • Post-liver-transplant CMV colitis: low-grade fever + diarrhoea + inclusion bodies on biopsy [6][7]
  • Congenital CMV: IUGR, microcephaly, periventricular calcification, sensorineural hearing loss, hepatosplenomegaly, petechiae ("blueberry muffin baby")
  • CMV retinitis: classical in AIDS with CD4 < 50; "pizza pie" fundoscopy (haemorrhages + exudates) [8]
Diagnosis
  • PBS: atypical lymphocytes (DDx: EBV, HIV, acute viral hepatitis, Mycoplasma, toxoplasmosis, drug reaction) [4][9]
  • CMV pp65 antigenaemia: buffy coat immunostaining; semi-quantitative; used in solid organ transplant recipients [1]
  • CMV viral load by PCR (EDTA whole blood): used in BMT recipients with low WBC for preemptive therapy [1]
  • Histology: "owl-eye" intranuclear inclusion bodies on biopsy (e.g. colonic biopsy) [6][7]
  • Serology: IgM/IgG seroconversion (limited value in I/C; useful for congenital CMV in neonate)
  • "Students did poorly since they did not understand the difference between CMV antigenemia and CMV seropositivity" [3]
Treatment
  • First-line: IV ganciclovir (or PO valganciclovir) — nucleoside analogue requiring viral UL97 kinase for phosphorylation
  • Second-line: foscarnet (pyrophosphate analogue; nephrotoxic) — for ganciclovir-resistant CMV (UL97 mutation)
  • Cidofovir: alternative if both above fail; dose-limiting nephrotoxicity
  • Key SE of ganciclovir: myelosuppression (neutropenia, thrombocytopenia)
  • Preemptive strategy in transplant: monitor viral load → treat when rising above threshold before clinical disease
Prevention
  • CMV-seronegative blood products indicated for: CMV-seroneg pregnant women, neonates, CMV-seroneg transplant recipients [3]
  • If CMV-seroneg blood unavailable → use leukodepleted blood components [3]
  • Prophylaxis in high-risk transplant (D+/R−): valganciclovir
  • No licensed vaccine currently available
  • Universal screening for congenital CMV: hearing screening in newborns
Classic traps
  • CMV mono vs EBV mono: CMV = heterophile-Ab NEGATIVE (monospot −), less pharyngitis/LAP [4]
  • CMV antigenemia ≠ CMV seropositivity: antigenemia = active viral replication; seropositivity = past exposure (>90% in HK) [3]
  • Post-transplant diarrhoea with inclusion bodies on colonic biopsy → CMV, NOT Streptococcus mitis or Talaromyces [6][7]
  • Congenital CMV vs congenital toxoplasmosis: CMV = periventricular calcification; Toxo = diffuse/scattered calcification
  • NK-cell lymphoma (nasal) is associated with EBV, NOT CMV [10]
  • Neutropenic fever at day 10 post-chemo: think bacteria (Strep viridans) or fungi, NOT CMV [11]

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