Human herpes simplex viruses (HSV-1 and HSV-2) cause significant morbidity and mortality in neonatal and immunocompromised populations. HSVs are cytolytic viruses which have profound impacts on their host cells. The broad, long-term objective of our research program is to understand the regulation of HSV infection in human cells. This research plan focuses on two representative, highly modified HSV proteins. The hypothesis being tested is that viral protein modification acts as a means to regulate HSV replication. The goal of the first specific aim is to use a combination of molecular genetics and cell biology techniques to determine the function of modified, nuclear VP22 during HSV infection. In the second specific aim, the goal is to combine genetic and physical biochemical analyses to correlate ICP22 posttranslational modifications with its function as a regulator of HSV replication. These studies will determine whether viral protein modifications are necessary processes in the replication of HSV. Since the focus is on key features of virus-host interactions, our findings are of importance to studies of other related human viruses. In the long term, this research will help define the molecular basis of regulation of the life cycle of these important human pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038873-09
Application #
6862771
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Beisel, Christopher E
Project Start
1996-09-01
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
9
Fiscal Year
2005
Total Cost
$339,000
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Cotter, Christopher R; Kim, Won-keun; Nguyen, Marie L et al. (2011) The virion host shutoff protein of herpes simplex virus 1 blocks the replication-independent activation of NF-ýýB in dendritic cells in the absence of type I interferon signaling. J Virol 85:12662-72
Bowles, Robert N; Blaho, John A (2011) A truncation mutation of the neurovirulence ICP22 protein produced by a recombinant HSV-1 generated by bacterial artificial chromosome technology targets infected cell nuclei. J Neurovirol 17:559-69
Cotter, Christopher R; Nguyen, Marie L; Yount, Jacob S et al. (2010) The virion host shut-off (vhs) protein blocks a TLR-independent pathway of herpes simplex virus type 1 recognition in human and mouse dendritic cells. PLoS One 5:e8684
Blaho, John A (2010) Oncoapoptosis: a novel molecular therapeutic for cancer treatment. IUBMB Life 62:87-91
Schlegel, Elisabeth F M; Blaho, John A (2009) A conserved carboxy-terminal domain in the major tegument structural protein VP22 facilitates virion packaging of a chimeric protein during productive herpes simplex virus 1 infection. Virology 387:449-58
Nguyen, Marie L; Blaho, John A (2009) Cellular players in the herpes simplex virus dependent apoptosis balancing act. Viruses 1:965-78
Cotter, Christopher R; Blaho, John A (2009) Detection of herpes simplex virus dependent apoptosis. Methods Mol Biol 559:371-87
Lopez, Maria R; Schlegel, Elisabeth F M; Wintersteller, Sandra et al. (2008) The major tegument structural protein VP22 targets areas of dispersed nucleolin and marginalized chromatin during productive herpes simplex virus 1 infection. Virus Res 136:175-88