Human cytomegalovirus UL78 is a nuclear-localized GPCR necessary for efficient reactivation from latent infection in CD34⁺ hematopoietic progenitor cells.

ABSTRACT: Human cytomegalovirus (HCMV) is a ubiquitous pathogen that persists throughout the lifetime of the host due to the establishment of latency. HCMV encodes four putative G protein-coupled receptors (GPCRs): US27, US28, UL33, and UL78. A definitive role for UL78 in HCMV infection has yet to be elucidated. Utilizing an in vitro CD34⁺ hematopoietic progenitor cell (HPC) model, we demonstrate that a recombinant virus lacking UL78 protein expression fails to efficiently reactivate from latent infection. Furthermore, we show that UL78 preferentially couples to the Gα_i family of G proteins and that a recombinant HCMV containing mutations in the UL78 G protein-coupling DRL motif also fails to reactivate from latent infection. Together, our findings indicate that Gα_i

SUBMITTER: Medica S 

PROVIDER: S-EPMC12645970 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature