Cytomegalovirus replication (CMV replication)

Cytomegalovirus (CMV) replication is the multi-stage biological process by which the human cytomegalovirus (HCMV), a double-stranded DNA virus of the Herpesviridae family, produces new infectious virions [12, 17]. This process is a primary therapeutic target for managing CMV infections, which are a major cause of morbidity and mortality in immunocompromised individuals, such as transplant recipients and patients with AIDS, as well as a leading cause of congenital birth defects [5, 10]. The replication cycle involves several essential viral proteins that serve as specific molecular targets, including the viral DNA polymerase (UL54), the terminase complex (UL56/UL89/UL51), and the UL97 protein kinase [1, 16]. Traditional antiviral drugs like ganciclovir and foscarnet inhibit the DNA polymerase to prevent genome synthesis, while newer agents like letermovir and maribavir target the terminase complex and UL97 kinase, respectively, to disrupt viral packaging and assembly [1, 6]. CMV replication is highly dynamic in vivo and its inhibition is critical for preventing clinical complications such as retinitis, pneumonia, and organ rejection [14, 16]. Therapeutic challenges include significant drug toxicities, such as myelosuppression and nephrotoxicity, and the emergence of drug-resistant viral strains through mutations in the targeted viral genes [1, 16].

Other names

HCMV replicationHuman cytomegalovirus replicationCMV DNA replicationCytomegalovirus life cycle

Inhibition of viral DNA polymerase (UL54), inhibition of the viral terminase complex (UL56), inhibition of the UL97 protein kinase, and antisense inhibition of immediate-early 2 (IE2) mRNA translation.