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Human cytomegalovirus lytic infection inhibits replication-dependent histone synthesis and requires stem loop binding protein function. Proc Natl Acad Sci U S A 2022 04 05;119(14):e2122174119

Date

03/29/2022

Pubmed ID

35344424

Pubmed Central ID

PMC9169081

DOI

10.1073/pnas.2122174119

Scopus ID

2-s2.0-85127264685

Abstract

Replication-dependent (RD) histones are deposited onto human cytomegalovirus (HCMV) genomes at the start of infection. We examined how HCMV affects the de novo production of RD histones and found that viral infection blocked the accumulation of RD histone mRNAs that normally occurs during the S phase. Furthermore, RD histone mRNAs present in HCMV-infected cells did not undergo the unique 3a?? processing required for their normal nuclear export and translation. The protein that orchestrates processing in the nucleus, stem loopa??binding protein (SLBP), was found predominantly in the cytoplasm, and RD histone proteins were not de novo synthesized in HCMV-infected cells. Intriguingly, however, we found that SLBP was required for the efficient synthesis and assembly of infectious progeny virions. We conclude that HCMV infection attenuates RD histone mRNA accumulation and processing and the de novo protein synthesis of the RD histones, while utilizing SLBP for an alternative purpose to support infectious virion production.

Author List

Albright ER, Morrison K, Ranganathan P, Carter DM, Nishikiori M, Lee JH, Slayton MD, Ahlquist P, Terhune SS, Kalejta RF

Author

Scott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Division
Cytomegalovirus
Cytomegalovirus Infections
DNA Replication
Histones
Humans
Virus Replication