Human herpesvirus 5 (Human cytomegalovirus) (HHV-5 (HCMV))

Human herpesvirus 5 (HHV-5), more commonly known as Human cytomegalovirus (HCMV), is a large, enveloped double-stranded DNA virus belonging to the Betaherpesvirinae subfamily (StatPearls, 2023). It is a ubiquitous pathogen that establishes a lifelong latent infection in various cell types, including myeloid progenitor cells and monocytes, following primary exposure (Wikipedia, 2024). While typically asymptomatic in immunocompetent individuals, HHV-5 is a major cause of morbidity and mortality in immunocompromised patients, such as organ transplant recipients and those with HIV/AIDS, where it can cause severe end-organ diseases like retinitis, pneumonitis, and colitis (NIH, 2023). Furthermore, it is the leading cause of congenital viral infection worldwide, potentially resulting in permanent neurodevelopmental disabilities and sensorineural hearing loss in neonates (PubMed, 2022). Pharmacological management involves targeting essential viral proteins, most notably the DNA polymerase (UL54), the terminase complex, and the UL97 protein kinase (PubChem, 2024). Although effective, current therapies are often limited by significant toxicities, such as bone marrow suppression and renal impairment, and the frequent emergence of drug-resistant viral strains (Journal of Clinical Virology, 2023).

Other names

Human cytomegalovirusHCMVCMVCytomegalic inclusion virus

Drugs targeting Human herpesvirus 5 primarily act by inhibiting viral DNA replication and assembly. Traditional nucleoside and nucleotide analogs like ganciclovir and cidofovir, as well as the pyrophosphate analog foscarnet, inhibit the viral DNA polymerase (UL54) (StatPearls, 2023). Newer therapeutic classes include letermovir, which inhibits the viral terminase complex (UL56/UL89/UL51) required for DNA packaging, and maribavir, which inhibits the UL97 protein kinase, a multifunctional enzyme essential for viral nuclear egress and DNA synthesis (FDA, 2021; PubMed, 2022).