Induction of potent local cellular immunity with low dose X4 SHIV{sub SF33A} vaginal exposure
- Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Ave., 7th Floor, New York, NY 10016 (United States)
- CONRAD, Eastern Virginia Medical School, 1611 North Kent Street Suite 806, Arlington, VA 22209 (United States)
- Tulane National Primate Research Center, Tulane University Medical Center, 18702 Three Rivers Road, Covington, LA 70433 (United States)
- Institut Pasteur, Unite d'Immunologie Virale, 28 rue du Dr roux, 75724 Paris Cedex 15 (France)
Intravaginal inoculation of rhesus macaques with varying doses of the CXCR4 (X4)-tropic SHIV{sub SF33A} isolate revealed a threshold inoculum for establishment of systemic virus infection and a dose dependency in overall viral burden and CD4+ T cell depletion. While exposure to inoculum size of 1000 or greater 50% tissue infectious dose (TCID{sub 50}) resulted in high viremia and precipitous CD4+ T cell loss, occult infection was observed in seven of eight macaques exposed to 500 TCID{sub 50} of the same virus. The latter was characterized by intermittent detection of low level virus with no evidence of seroconversion or CD4+ T cell decline, but with signs of an ongoing antiviral T cell immune response. Upon vaginal re-challenge with the same limiting dose 11-12 weeks after the first, classic pathogenic X4 SHIV{sub SF33A} infection was established in four of the seven previously exposed seronegative macaques, implying enhanced susceptibility to systemic infection with prior exposure. Pre-existing peripheral SIV gag-specific CD4+ T cells were more readily demonstrable in macaques that became systemically infected following re-exposure than those that were not. In contrast, early presence of circulating polyfunctional cytokine secreting CD8+ T cells or strong virus-specific proliferative responses in draining lymph nodes and in the gut associated lymphoid tissue (GALT) following the first exposure was associated with protection from systemic re-infection. These studies identify the gut and lymphoid tissues proximal to the genital tract as sites of robust CD8 T lymphocyte responses that contribute to containment of virus spread following vaginal transmission.
- OSTI ID:
- 21077981
- Journal Information:
- Virology, Vol. 367, Issue 1; Other Information: DOI: 10.1016/j.virol.2007.05.021; PII: S0042-6822(07)00372-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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