Summary auto-generated
This study investigates how herpesvirus saimiri (HVS) manipulates host cell machinery during infection. The researchers focused on ORF 57, a viral gene product similar to herpes simplex virus ICP27, which previous work showed could regulate viral gene expression through post-transcriptional mechanisms, particularly affecting genes containing introns. Using immunofluorescence microscopy in infected COS-7 cells, the authors demonstrated that HVS infection causes redistribution of SC-35, a spliceosome assembly factor essential for removing introns from pre-mRNA. Critically, they showed that SC-35 colocalizes with the ORF 57 protein in distinct nuclear domains. To establish causation, they transfected cells with ORF 57 alone, which was sufficient to cause SC-35 redistribution without viral infection. Similar redistribution was observed for U2 snRNP, another spliceosome component. These findings suggest ORF 57 functions analogously to ICP27 by relocating key splicing machinery, likely explaining how the virus suppresses expression of viral genes containing introns while potentially promoting expression of intron-free transcripts needed for viral replication.
Key findings
- HVS infection causes redistribution of the spliceosome component SC-35 from its normal dispersed nuclear pattern to distinct punctate foci
- ORF 57 protein colocalizes with redistributed SC-35 and other spliceosome factors in the infected cell nucleus
- Expression of ORF 57 protein alone is sufficient to cause spliceosome component redistribution without requiring other viral gene products
- ORF 57 likely functions similarly to HSV-1 ICP27 in disrupting host cell splicing machinery to regulate viral and host gene expression
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Abstract
The herpesvirus saimiri (HVS) gene product encoded by ORF 57 shares limited C-terminal similarity with herpes simplex virus 1 ICP27, a protein that has been demonstrated to be involved in the inhibition of host-cell splicing and is responsible for the redistribution of components of the spliceosome. It has previously been shown that ORF 57 can either activate or repress viral gene expression by a post-transcriptional mechanism. Furthermore, repression of gene expression by ORF 57 is dependent on the presence of an intron within the target gene coding region. In this report, it is shown that HVS infection results in the redistribution of the SC-35 splicing factor in the infected cell nucleus. Furthermore, the redistributed SC-35 colocalized with the ORF 57 protein product and expression of the protein alone was sufficient to cause the redistribution of the spliceosome components. These results suggest that the mechanism by which ORF 57 down-regulates expression of intron-containing genes involves the redistribution of the spliceosome complex.