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 FY2010 we found that Tregs are predominantly functional in the lymphoid tissues and not in organs such as the liver where virus is much better controlled by CD8+ T cell responses. This knowledge is important because it shows us which tissue to study to determine the conditions necessary for virus clearance, and also leads us to possible therapeutic interventions such as re-targeting active CD8+ T cells from the liver to the spleen and other sites of viral replication.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2010
Total Cost
$691,232
Indirect Cost
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State
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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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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
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