Differential innate immune responses to low or high dose oral SIV challenge in Rhesus macaques

Andre Durudas, Hui Ling Chen, Melanie A. Gasper, Vasudha Sundaravaradan, Jeffrey M. Milush, Guido Silvestri, Welkin Johnson, Luis D. Giavedoni, Donald L. Sodora

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    14 Scopus citations

    Abstract

    Mucosal transmission of HIV predominately occurs during sexual intercourse or breast-feeding and generally results in a successful infection from just one or few founder virions. Here we assessed the impact of viral inoculum size on both viral and immune events within two groups of Rhesus macaques that were non-traumatically, orally inoculated with either multiple low (1000 to 4000 TCID 50) or high (100,000 TCID 50) doses of SIV. In agreement with previous studies, more diverse SIV variants were observed in macaques following infection with high dose oral SIV compared to a low dose challenge. In peripheral blood cells, the immune gene transcript levels of CXCL9, IFNγ, TNFα and IL10 remained similar to uninfected macaques. In contrast, OAS and CXCL10 were upregulated following SIV infection in both the high and low dosed macaques, with a more rapid kinetics (detectable by 7 days) following the high SIV dose challenge. In peripheral lymph nodes, an increase in CXCL10 was observed irrespective of viral dose while CXCL9 and OAS were differentially regulated in the two SIV dosed groups. Magnetic bead sorting of CD3+, CD14+ and CD3-/CD14- cells from peripheral blood identified the increase in OAS expression primarily within CD14+ monocytes, whereas the CXCL10 expression was primarily in CD3+ T cells. These findings provide insights into the impact of SIV challenge dose on viral and innate immune factors, which has the potential to inform future SIV/HIV vaccine efficacy trials in which vaccinated hosts have the potential to be infected with a range of viral challenge doses.

    Original languageEnglish (US)
    Pages (from-to)276-288
    Number of pages13
    JournalCurrent HIV Research
    Volume9
    Issue number5
    DOIs
    StatePublished - Oct 17 2011

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    Keywords

    • AIDS
    • HIV
    • Innate immune responses
    • Low dose
    • Oral transmission
    • Rhesus macaques
    • SIV

    ASJC Scopus subject areas

    • Infectious Diseases
    • Virology

    Cite this

    Durudas, A., Chen, H. L., Gasper, M. A., Sundaravaradan, V., Milush, J. M., Silvestri, G., Johnson, W., Giavedoni, L. D., & Sodora, D. L. (2011). Differential innate immune responses to low or high dose oral SIV challenge in Rhesus macaques. Current HIV Research, 9(5), 276-288. https://doi.org/10.2174/157016211797635928