Abstract

The purpose of this application is to examine the regulation of virus infections by natural killer (NK) cells and other natural effector systems and to study how the NK cells interact with specific immune mechanisms and interferon (IFN) to bring about clearance of virus infection. A variety of viral infections will be used in the mouse model, including infections with lymphocytic choriomeningitis, murine cytomegalo, herpes simplex, vaccinia, Pichinde, and mouse hepatitis (MHV) viruses. These and several other viruses and variants will be screened for sensitivity to NK cells in vivo, and this will be correlated with their sensitivity to NK cell mediated lysis in vitro, with the aim of determining what property of a virus confers sensitivity to NK cells. The regulation of virus infections by lymphokine activated killer (LAK) cells will be examined, with the aim of developing therapeutic protocols to control virus infections with these cells. The regulation of mouse hepatitis virus infection by a recently discovered cytotoxic effect of B cells will be examined. This work should help define the parameters of natural immunity to virus infections and will determine whether natural effector cells can be used to control infections therapeutically.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017672-14
Application #
3127370
Study Section
Experimental Immunology Study Section (EI)
Project Start
1980-07-01
Project End
1994-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
14
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Che, Jenny W; Daniels, Keith A; Selin, Liisa K et al. (2017) Heterologous Immunity and Persistent Murine Cytomegalovirus Infection. J Virol 91:
Nayar, Ribhu; Schutten, Elizabeth; Jangalwe, Sonal et al. (2015) IRF4 Regulates the Ratio of T-Bet to Eomesodermin in CD8+ T Cells Responding to Persistent LCMV Infection. PLoS One 10:e0144826
Rydyznski, Carolyn; Daniels, Keith A; Karmele, Erik P et al. (2015) Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells. Nat Commun 6:6375
Waggoner, Stephen N; Daniels, Keith A; Welsh, Raymond M (2014) Therapeutic depletion of natural killer cells controls persistent infection. J Virol 88:1953-60
Mishra, Rabinarayan; Welsh, Raymond; Szomolanyi-Tsuda, Eva (2014) NK cells and virus-related cancers. Crit Rev Oncog 19:107-19
Kapoor, Varun N; Shin, Hyun Mu; Cho, Ok Hyun et al. (2014) Regulation of tissue-dependent differences in CD8+ T cell apoptosis during viral infection. J Virol 88:9490-503
Nayar, Ribhu; Schutten, Elizabeth; Bautista, Bianca et al. (2014) Graded levels of IRF4 regulate CD8+ T cell differentiation and expansion, but not attrition, in response to acute virus infection. J Immunol 192:5881-93
Urban, Stina L; Welsh, Raymond M (2014) Out-of-sequence signal 3 as a mechanism for virus-induced immune suppression of CD8 T cell responses. PLoS Pathog 10:e1004357
Welsh, Raymond M; Waggoner, Stephen N (2013) NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections. Virology 435:37-45
Mishra, Rabinarayan; Polic, Bojan; Welsh, Raymond M et al. (2013) Inflammatory cytokine-mediated evasion of virus-induced tumors from NK cell control. J Immunol 191:961-70

Showing the most recent 10 out of 119 publications