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Journal of Virology, December 2008, p. 12535-12542, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.00881-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Vesicular Stomatitis Virus Matrix Protein Impairs CD1d-Mediated Antigen Presentation through Activation of the p38 MAPK Pathway{triangledown}

Gourapura J. Renukaradhya, Masood A. Khan, Daniel Shaji, and Randy R. Brutkiewicz*

Department of Microbiology and Immunology, Indiana University School of Medicine, Walther Oncology Center, Indianapolis, Indiana 46202, and the Walther Cancer Institute, Indianapolis, Indiana 46208

Received 25 April 2008/ Accepted 11 September 2008

Natural killer T (NKT) cells are unique T lymphocytes that recognize CD1d-bound lipid antigens and play an important role in both innate and acquired immune responses against infectious diseases and tumors. We have already shown that a vesicular stomatitis virus (VSV) infection results in the rapid inhibition of murine CD1d-mediated antigen presentation to NKT cells. In the present study, it was found that the VSV matrix (VSV-M) protein is an important element in this decrease in antigen presentation postinfection. The VSV-M protein altered the intracellular distribution of murine CD1d molecules, resulting in qualitative (but not quantitative) changes in cell surface CD1d expression. The M protein was distributed throughout the infected cell, and it was found to activate the mitogen-activated protein kinase (MAPK) p38 very early postinfection. Infection of CD1d+ cells with a temperature-sensitive VSV-M mutant at the nonpermissive temperature both substantially reversed the inhibition of antigen presentation by CD1d and delayed the activation of p38. Thus, the VSV-M protein plays an important role in permitting the virus to evade important components of the innate immune response by regulating specific MAPK pathways.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Indiana University School of Medicine, Walther Oncology Center, 950 W Walnut St., Bldg. R2, Rm. 302, Indianapolis, IN 46202-5181. Phone: (317) 274-7589. Fax: (317) 274-7592. E-mail: rbrutkie{at}iupui.edu

{triangledown} Published ahead of print on 24 September 2008.


Journal of Virology, December 2008, p. 12535-12542, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.00881-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.