Herpes simplex virus 2 (HSV-2) is a common human pathogen that causes painful, recurrent genital lesions in adults and disseminated disease in newborns. Seroprevalence among adults is estimated at 22% in the United States and as up to 75% in some African countries. HSV-2 encodes a protein kinase, UL13 important at almost all stages of the virus replication cycle. UL13-deficient mutants are profoundly attenuated in mouse models of infection. The kinase activity of UL13 has been linked to the modification of proteins that promote tegument dissociation and late gene expression. HSV infection modulates the cell cycle and causes dissolution of the nuclear lamins. UL13 kinase activity has been implicated in regulation of the former but the effect of U1_13 kinase activity on the nuclear lamin network is unknown. How UL13 recognizes viral and cellular substrates to modulate these viral and cellular processes is also unknown. The objectives of this research are to define the UL13 substrate recognition motif by using two supporting approaches 1) mutation of candidate motif residues in their native context and 2) synthesis of substrate peptides containing wild-type and mutant target motifs. In addition, an in vitro system will be used to determine the effects of UL13 on the nuclear lamin matrix. The long-range goal is to determine the contribution of UL13 kinase activity to virus replication and pathogenesis by constructing and testing a UL13 kinase activity-deficient virus.
| Cano-Monreal, Gina L; Wylie, Kristine M; Cao, Feng et al. (2009) Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins. Virology 392:137-47 |
| Cano-Monreal, Gina L; Tavis, John E; Morrison, Lynda A (2008) Substrate specificity of the herpes simplex virus type 2 UL13 protein kinase. Virology 374:1-10 |
