Abstract

Chronic viral infections can lead to death if the virus is HIV, or even if the virus is usually innocuous but the person becomes immunosuppressed from another viral infection or treatment for cancer. Previous studies in our lab showed that regulatory T cells (Tregs) can contribute to the establishment of chronic infections by suppressing anti-viral CD8+ T cell responses. These studies were done in mice infected with Friend retrovirus and subsequently shown for HIV and other viruses as well. In this reporting period we provided direct proof using conditional knockout mice that Tregs suppressed CD8+ T cell responses leading to higher virus loads. By reducing levels of Tregs we were able to restore CD8+ T cell responses and decrease chronic virus loads. This knowledge is important because it indicates a possible new therapeutic intervention for chronic infections such as HIV.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001100-04
Application #
8556009
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2012
Total Cost
$311,382
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Halemano, Kalani; Guo, Kejun; Heilman, Karl J et al. (2014) Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral infection. Proc Natl Acad Sci U S A 111:7759-64
Messer, Ronald J; Lavender, Kerry J; Hasenkrug, Kim J (2014) Mice of the resistant H-2(b) haplotype mount broad CD4(+) T cell responses against 9 distinct Friend virus epitopes. Virology 456-457:139-44
Joedicke, Jara J; Zelinskyy, Gennadiy; Dittmer, Ulf et al. (2014) CD8+ T cells are essential for controlling acute friend retrovirus infection in C57BL/6 mice. J Virol 88:5200-1
Li, Sam X; Barrett, Bradley S; Heilman, Karl J et al. (2014) Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo. J Immunol 193:306-16
Thorborn, Georgina; Ploquin, Mickaël J; Eksmond, Urszula et al. (2014) Clonotypic composition of the CD4+ T cell response to a vectored retroviral antigen is determined by its speed. J Immunol 193:1567-77
Lavender, Kerry J; Messer, Ronald J; Race, Brent et al. (2014) Production of bone marrow, liver, thymus (BLT) humanized mice on the C57BL/6 Rag2(-/-)?c(-/-)CD47(-/-) background. J Immunol Methods 407:127-34
Manzke, Nora; Akhmetzyanova, Ilseyar; Hasenkrug, Kim J et al. (2013) CD4+ T cells develop antiretroviral cytotoxic activity in the absence of regulatory T cells and CD8+ T cells. J Virol 87:6306-13
Lavender, Kerry J; Pang, Wendy W; Messer, Ronald J et al. (2013) BLT-humanized C57BL/6 Rag2-/-?c-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection. Blood 122:4013-20
Harper, Michael S; Barrett, Bradley S; Smith, Diana S et al. (2013) IFN-? treatment inhibits acute Friend retrovirus replication primarily through the antiviral effector molecule Apobec3. J Immunol 190:1583-90
Kubinak, J L; Ruff, J S; Cornwall, D H et al. (2013) Experimental viral evolution reveals major histocompatibility complex polymorphisms as the primary host factors controlling pathogen adaptation and virulence. Genes Immun 14:365-72

Showing the most recent 10 out of 25 publications