TY - JOUR
T1 - The viral packaging motor potentiates Kaposi’s sarcoma-associated herpesvirus gene expression late in infection
AU - McCollum, Chloe O.
AU - Didychuk, Allison L.
AU - Liu, Dawei
AU - Murray-Nerger, Laura A.
AU - Cristea, Ileana M.
AU - Glaunsinger, Britt A.
N1 - Publisher Copyright:
© 2023 McCollum et al.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85159242636&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159242636&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1011163
DO - 10.1371/journal.ppat.1011163
M3 - Article
C2 - 37068108
AN - SCOPUS:85159242636
SN - 1553-7366
VL - 19
JO - PLoS pathogens
JF - PLoS pathogens
IS - 4
M1 - e1011163
ER -