The aryl hydrocarbon receptor facilitates the human cytomegalovirus-mediated G1/S block to cell cycle progression.

TitleThe aryl hydrocarbon receptor facilitates the human cytomegalovirus-mediated G1/S block to cell cycle progression.
Publication TypeJournal Article
Year of Publication2021
AuthorsNaseri-Nosar, P, Nogalski, MT, Shenk, T
JournalProc Natl Acad Sci U S A
Volume118
Issue12
Date Published2021 03 23
ISSN1091-6490
KeywordsCell Cycle, Cell Division, Cytomegalovirus, Cytomegalovirus Infections, G1 Phase, Host-Pathogen Interactions, Humans, Kynurenine, Ligands, Receptors, Aryl Hydrocarbon
Abstract

<p>The tryptophan metabolite, kynurenine, is known to be produced at elevated levels within human cytomegalovirus (HCMV)-infected fibroblasts. Kynurenine is an endogenous aryl hydrocarbon receptor (AhR) ligand. Here we show that the AhR is activated following HCMV infection, and pharmacological inhibition of AhR or knockdown of AhR RNA reduced the accumulation of viral RNAs and infectious progeny. RNA-seq analysis of infected cells following AhR knockdown showed that the receptor alters the levels of numerous RNAs, including RNAs related to cell cycle progression. AhR knockdown alleviated the G1/S cell cycle block that is normally instituted in HCMV-infected fibroblasts, consistent with its known ability to regulate cell cycle progression and cell proliferation. In sum, AhR is activated by kynurenine and perhaps other ligands produced during HCMV infection, it profoundly alters the infected-cell transcriptome, and one outcome of its activity is a block to cell cycle progression, providing mechanistic insight to a long-known element of the virus-host cell interaction.</p>

DOI10.1073/pnas.2026336118
Alternate JournalProc Natl Acad Sci U S A
PubMed ID33723080
PubMed Central IDPMC8000196
Grant ListR21 AI142520 / AI / NIAID NIH HHS / United States