Cytomegalovirus (CMV, HHV‑5) is a large enveloped double‑stranded DNA virus of the Betaherpesvirinae subfamily. It infects a wide range of cell types and establishes latent infection in myeloid progenitor cells. While asymptomatic in most immunocompetent hosts, CMV is a major cause of congenital infection and serious disease in immunosuppressed individuals.
Virology and Latency
CMV has one of the largest genomes among human herpesviruses, encoding over 200 proteins and numerous noncoding RNAs. Its icosahedral nucleocapsid is surrounded by a proteinaceous tegument and a lipid envelope bearing glycoprotein complexes (gB, gH/gL/gO, gM/gN) that mediate attachment and entry into fibroblasts, epithelial cells, endothelial cells and leukocytes. The virus binds to heparan sulfate and cell surface integrins before fusion. Replication occurs in the nucleus with an extended replication cycle; infected cells become enlarged with intranuclear “owl’s eye” inclusions. CMV expresses sequential immediate early, early and late genes, including the UL54 DNA polymerase targeted by antiviral drugs. Latency is established in CD34+ hematopoietic progenitors and monocytes, where viral gene expression is highly restricted. Differentiation or inflammation can trigger reactivation, leading to production of infectious virions. The immune system, particularly cytotoxic T cells and NK cells, plays a critical role in controlling CMV, but the virus encodes multiple immunomodulatory proteins to evade detection.
Clinical Spectrum and Management
Congenital CMV infection results from transplacental transmission during maternal viremia and is the leading non‑genetic cause of sensorineural hearing loss. Affected infants may present with microcephaly, periventricular calcifications, seizures, jaundice, hepatosplenomegaly and chorioretinitis. In immunocompetent adults, primary infection is often subclinical or causes a mononucleosis‑like illness with fever, malaise and lymphocytosis. In contrast, reactivation or primary infection in immunocompromised patients can cause severe end‑organ disease including retinitis in people with AIDS, colitis and esophagitis in transplant recipients, interstitial pneumonia, hepatitis and encephalitis. Diagnosis relies on PCR, antigenemia assays or viral culture. Treatment includes nucleoside analogues such as ganciclovir and its oral prodrug valganciclovir, which inhibit viral DNA polymerase; foscarnet and cidofovir are alternatives for resistant strains. Prevention in transplant settings involves prophylactic or pre‑emptive antiviral therapy and donor‑recipient serostatus matching. Vaccine development is ongoing but none are yet approved. CMV infection is ubiquitous and usually harmless, yet it poses significant risks to developing fetuses and immunosuppressed patients. Understanding its biology and the immune response has enabled effective antiviral treatments, but a safe vaccine remains an unmet need. Related Terms: congenital infection, ganciclovir, betaherpesvirus, latency, immunocompromised