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.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2011
Total Cost
$563,953
Indirect Cost
City
State
Country
Zip Code
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
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