Abstract
Murine gammaherpesvirus (MHV) 68, a natural pathogen of field mice, is related to human gammaherpesviruses, Epstein-Barr virus (EBV; human herpesvirus 4) and Kaposi’s sarcomaassociated herpesvirus (KSHV; human herpesvirus 8). The ORF35 of MHV-68 and its homologues of EBV and KSHV are located in the gene cluster composed of ORF34-ORF38 in which each gene overlaps with adjacent genes. Although MHV-68 ORF35 was reported to be an essential gene, its function during infection is presently unknown. In this study, we show, by analysing ORF35-transfected cells, that three serine residues in the C terminus are responsible for the phosphorylation and that the ORF35 protein forms homo-oligomers via a predicted coiled-coil motif. The ORF35 protein expressed by transfection was preferentially located in the cytoplasm of cells uninfected or infected with MHV-68. The recombinant virus lacking ORF35 (35S virus) exhibited genome replication and expression of lytic proteins comparable to those of the WT virus, but reduced levels of virus production, suggesting that the ORF35 protein acts at the virion assembly and/or egress step. Lytic replication in the lung after intranasal infection and the frequency of ex vivo reactivation from latency after intraperitoneal infection were lower in 35S virus-infected mice than in mice infected with the WT or marker-reverted virus. Our results indicate that ORF35 is not essential for MHV-68 lytic replication, but plays an important role in efficient viral replication and reactivation from latency.
| Original language | English |
|---|---|
| Pages (from-to) | 3624-3634 |
| Number of pages | 11 |
| Journal | Journal of General Virology |
| Volume | 96 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2015 |
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All Science Journal Classification (ASJC) codes
- Virology
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Murine gammaherpesvirus 68 ORF35 is required for efficient lytic replication and latencyshin-ichi hikita correspondence. / Hikita, Shin Ichi; Yanagi, Yusuke; Ohno, Shinji.
In: Journal of General Virology, Vol. 96, No. 12, 12.2015, p. 3624-3634.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Murine gammaherpesvirus 68 ORF35 is required for efficient lytic replication and latencyshin-ichi hikita correspondence
AU - Hikita, Shin Ichi
AU - Yanagi, Yusuke
AU - Ohno, Shinji
PY - 2015/12
Y1 - 2015/12
N2 - Murine gammaherpesvirus (MHV) 68, a natural pathogen of field mice, is related to human gammaherpesviruses, Epstein-Barr virus (EBV; human herpesvirus 4) and Kaposi’s sarcomaassociated herpesvirus (KSHV; human herpesvirus 8). The ORF35 of MHV-68 and its homologues of EBV and KSHV are located in the gene cluster composed of ORF34-ORF38 in which each gene overlaps with adjacent genes. Although MHV-68 ORF35 was reported to be an essential gene, its function during infection is presently unknown. In this study, we show, by analysing ORF35-transfected cells, that three serine residues in the C terminus are responsible for the phosphorylation and that the ORF35 protein forms homo-oligomers via a predicted coiled-coil motif. The ORF35 protein expressed by transfection was preferentially located in the cytoplasm of cells uninfected or infected with MHV-68. The recombinant virus lacking ORF35 (35S virus) exhibited genome replication and expression of lytic proteins comparable to those of the WT virus, but reduced levels of virus production, suggesting that the ORF35 protein acts at the virion assembly and/or egress step. Lytic replication in the lung after intranasal infection and the frequency of ex vivo reactivation from latency after intraperitoneal infection were lower in 35S virus-infected mice than in mice infected with the WT or marker-reverted virus. Our results indicate that ORF35 is not essential for MHV-68 lytic replication, but plays an important role in efficient viral replication and reactivation from latency.
AB - Murine gammaherpesvirus (MHV) 68, a natural pathogen of field mice, is related to human gammaherpesviruses, Epstein-Barr virus (EBV; human herpesvirus 4) and Kaposi’s sarcomaassociated herpesvirus (KSHV; human herpesvirus 8). The ORF35 of MHV-68 and its homologues of EBV and KSHV are located in the gene cluster composed of ORF34-ORF38 in which each gene overlaps with adjacent genes. Although MHV-68 ORF35 was reported to be an essential gene, its function during infection is presently unknown. In this study, we show, by analysing ORF35-transfected cells, that three serine residues in the C terminus are responsible for the phosphorylation and that the ORF35 protein forms homo-oligomers via a predicted coiled-coil motif. The ORF35 protein expressed by transfection was preferentially located in the cytoplasm of cells uninfected or infected with MHV-68. The recombinant virus lacking ORF35 (35S virus) exhibited genome replication and expression of lytic proteins comparable to those of the WT virus, but reduced levels of virus production, suggesting that the ORF35 protein acts at the virion assembly and/or egress step. Lytic replication in the lung after intranasal infection and the frequency of ex vivo reactivation from latency after intraperitoneal infection were lower in 35S virus-infected mice than in mice infected with the WT or marker-reverted virus. Our results indicate that ORF35 is not essential for MHV-68 lytic replication, but plays an important role in efficient viral replication and reactivation from latency.
UR - http://www.scopus.com/inward/record.url?scp=84955583918&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955583918&partnerID=8YFLogxK
U2 - 10.1099/jgv.0.000310
DO - 10.1099/jgv.0.000310
M3 - Article
C2 - 26459827
AN - SCOPUS:84955583918
VL - 96
SP - 3624
EP - 3634
JO - Journal of General Virology
JF - Journal of General Virology
SN - 0022-1317
IS - 12
ER -