Multiple functions for ORF75c in Murid herpesvirus-4 infection

Gaspar, Miguel, Gill, Michael B, Losing, Jens-Bernhard, May, Janet S. and Stevenson, Philip G. (2008) Multiple functions for ORF75c in Murid herpesvirus-4 infection. PLoS ONE, 3 7: e2781.1-e2781.15. doi:10.1371/journal.pone.0002781


Author Gaspar, Miguel
Gill, Michael B
Losing, Jens-Bernhard
May, Janet S.
Stevenson, Philip G.
Title Multiple functions for ORF75c in Murid herpesvirus-4 infection
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2008-07-23
Year available 2008
Sub-type Article (original research)
DOI 10.1371/journal.pone.0002781
Open Access Status DOI
Volume 3
Issue 7
Start page e2781.1
End page e2781.15
Total pages 15
Place of publication San Francisco United States
Publisher Public Library of Science (PLoS)
Language eng
Abstract All gamma-herpesviruses encode at least one homolog of the cellular enzyme formyl-glycineamide-phosphoribosyl-amidotransferase. Murid herpesvirus-4 (MuHV-4) encodes 3 (ORFs 75a, 75b and 75c), suggesting that at least some copies have acquired new functions. Here we show that the corresponding proteins are all present in virions and localize to infected cell nuclei. Despite these common features, ORFs 75a and 75b did not substitute functionally for a lack of ORF75c, as ORF75c virus knockouts were severely impaired for lytic replication in vitro and for host colonization in vivo. They showed 2 defects: incoming capsids failed to migrate to the nuclear margin following membrane fusion, and genomes that did reach the nucleus failed to initiate normal gene expression. The latter defect was associated with a failure of in-coming virions to disassemble PML bodies. The capsid transport deficit seemed to be functionally more important, since ORF75c MuHV-4 infected both PML+ and PML- cells poorly. The original host enzyme has therefore evolved into a set of distinct and multi-functional viral tegument proteins. One important function is moving incoming capsids to the nuclear margin for viral genome delivery.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Clinical Medical Virology Centre Publications
 
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