Host cell signaling pathways regulating Cytomegalovirus replication

Host cell signaling pathways regulating Cytomegalovirus (CMV) replication represent a complex network of cellular processes that the virus hijacks to ensure successful infection and progeny production. Upon entry, CMV glycoproteins interact with host receptors such as EGFR and integrins, triggering mitogenic pathways including PI3K/Akt/mTOR and MAPK/ERK, which are critical for the expression of viral immediate-early (IE) genes and the metabolic reprogramming of the host cell (Source 1.1.1, 1.2.1). The virus also subverts the host DNA damage response (DDR) and heat shock response, specifically utilizing factors like HSF1 and ATM kinase to facilitate genome replication and prevent apoptosis (Source 1.1.2, 1.2.2). While standard-of-care therapies like ganciclovir target viral DNA polymerase, targeting these host pathways offers a novel approach to combat drug-resistant CMV strains. Host-targeting agents such as mTOR inhibitors (sirolimus) and DHODH inhibitors (leflunomide) have shown clinical and experimental efficacy by disrupting the cellular environment required for viral persistence and replication (Source 1.3.4).

Other names

HCMV-hijacked host signaling pathwaysHost factors in CMV replicationCellular signaling in CMV infectionHost-virus interaction pathways

Inhibition of host-derived kinases (e.g., mTOR, Raf), transcription factors (e.g., HSF1, NF-κB), or metabolic enzymes (e.g., DHODH) that the virus requires for gene expression, genome replication, and virion assembly.