• Clinical science

Cytomegalovirus infection


Infection with the cytomegalovirus (CMV or human herpes virus 5) is generally asymptomatic in immunocompetent hosts, but can cause mild mononucleosis-like symptoms. Like all Herpesviridae infections, CMV persists for the lifetime of its host; reactivation may therefore occur. Immunocompromised individuals (e.g., AIDS, post-transplantation) are especially at risk of illness following reactivation or initial infection, which can include severe manifestations such as CMV retinitis (risk of blindness) or life-threatening CMV pneumonia. Treatment with ganciclovir or valganciclovir should therefore begin promptly on clinical suspicion of a CMV infection.

Congenital CMV infection is discussed in another learning card.


  • Prevalence of CMV infection in the general population: 40–100%
  • Seroprevalence increases with age with more than 90% in individuals > 80 years

Epidemiological data refers to the US, unless otherwise specified.




  • CMV binds to integrins → activation of integrins → induction of cellular morphological changes → activation of transduction pathways such as FAK (focal adhesion kinase) and apoptotic pathways → cell damage → clinical manifestations depending on the organ/tissue affected.

Clinical features

CMV infection is usually asymptomatic. Severe manifestations occur in immunocompromised states (e.g., following organ transplantation, AIDS).

In immunocompetent patients

In immunocompromised patients

Among HIV-positive patients, manifestations of CMV disease usually occur when the CD4 count is ≤ 50!

One or more of the following clinical manifestations may be present:



  • CBC: relative lymphocytosis with > 10% atypical lymphocytes
  • Blood smear: : large atypical lymphocytes with intranuclear inclusion bodies that have an owl-eye appearance
  • Monospot (heterophile antibody) test: negative
  • Serological tests
  • Direct evidence of viremia: especially useful in immunosuppressed patients
    • PCR to detect CMV DNA in bodily fluids
    • Indirect immunofluorescence assay: pp-65 CMV antigens
  • Fundoscopy: retinal hemorrhages and cotton-wool spots (“pizza-pie” appearance)

Serological tests may be unreliable in immunosuppressed patients!



CMV infection Regimen Duration
CMV retinitis
  • At least 3–6 months
CMV colitis
  • 21–42 days
CMV esophagitis
CMV pneumonia
  • Until CD4 count > 100 cells/mm3 and symptoms improve
CMV encephalitis