Open AccessHuman cytomegalovirus lytic infection inhibits replication-dependent histone synthesis and requires stem loop binding protein function
Author(s) -
Emily R. Albright,
Kylee Morrison,
Padhma Ranganathan,
Dominique M. Carter,
Masaki Nishikiori,
Jeong-Hee Lee,
Mark Slayton,
Paul Ahlquist,
Scott S. Terhune,
Robert F. Kalejta
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2122174119
Subject(s) - biology , lytic cycle , histone , human cytomegalovirus , dna replication , histone h2a , microbiology and biotechnology , virology , dna , genetics , virus
Significance Until now, it was not known if, how, or why pathogenic human viruses might modulate thede novo production of the replication-dependent (RD) histone proteins that decorate their DNA genomes within infected cells. Our finding that human cytomegalovirus (HCMV) inhibits RD histone production affirms that a virus targets this fundamental cellular process. Furthermore, our revelation that HCMV induces, relocalizes, and then commandeers the stem loop–binding protein (SLBP) for a purpose other than RD histone synthesis to support productive replication illuminates the potential for other functions of this highly conserved protein. The critical nature of SLBP for HCMV infection and of RD histone synthesis for cellular DNA replication highlights this process as a target for future antiviral and chemotherapeutic interventions.