The viral packaging motor potentiates Kaposi's sarcoma-associated herpesvirus gene expression late in infection.

Publication Year
2023

Type

Journal Article
Abstract

β- and γ-herpesviruses transcribe their late genes in a manner distinct from host transcription. This process is directed by a complex of viral transcriptional activator proteins that hijack cellular RNA polymerase II and an unknown set of additional factors. We employed proximity labeling coupled with mass spectrometry, followed by CRISPR and siRNA screening to identify proteins functionally associated with the Kaposi's sarcoma-associated herpesvirus (KSHV) late gene transcriptional complex. These data revealed that the catalytic subunit of the viral DNA packaging motor, ORF29, is both dynamically associated with the viral transcriptional activator complex and potentiates gene expression late in infection. Through genetic mutation and deletion of ORF29, we establish that its catalytic activity potentiates viral transcription and is required for robust accumulation of essential late proteins during infection. Thus, we propose an expanded role for ORF29 that encompasses its established function in viral packaging and its newly discovered contributions to viral transcription and late gene expression in KSHV.

Journal
PLoS pathogens
Volume
19
Issue
4
Pages
e1011163
Date Published
04/2023
ISSN Number
1553-7374
Alternate Journal
PLoS Pathog
PMCID
PMC10138851
PMID
37068108