Baboon CD8 T cells suppress SIVmac infection in CD4 T cells through contact-dependent production of MIP-1α MIP-1β and RANTES

Veronica Obregon-Perko, Vida L. Hodara, Laura M. Parodi, Luis D. Giavedoni

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations

    Abstract

    Simian immunodeficiency virus (SIV) infection in rhesus macaques is often characterized by high viremia and CD4 T cell depletion. By contrast, SIV infection in African nonhuman primate natural hosts is typically nonpathogenic despite active viral replication. Baboons are abundant in Africa and have a geographical distribution that overlaps with natural hosts, but they do not harbor SIVs. Previous work has demonstrated baboons are resistant to chronic SIV infection and/or disease in vivo but the underlying mechanisms remain unknown. Using in vitro SIVmac infections, we sought to identify SIV restriction factors in baboons by comparing observations to the pathogenic rhesus macaque model. SIVmac replicated in baboon PBMC but had delayed kinetics compared to rhesus PBMC. However, SIVmac replication in baboon and rhesus isolated CD4 cells were similar to the kinetics seen for rhesus PBMC, demonstrating intracellular restriction factors do not play a strong role in baboon inhibition of SIVmac replication. Here, we show CD8 T cells contribute to the innate SIV-suppressive activity seen in naïve baboon PBMC. As one mechanism of restriction, we identified higher production of MIP-1α MIP-1β and RANTES by baboon PBMC. Contact between CD4 and CD8 T cells resulted in maximum production of these chemokines and suppression of viral replication, whereas neutralization of CCR5-binding chemokines in baboon PBMC increased viral loads. Our studies indicate baboon natural restriction of SIVmac replication is largely dependent on CD4-extrinsinc mechanisms mediated, in part, by CD8 T cells.

    Original languageEnglish (US)
    Pages (from-to)408-419
    Number of pages12
    JournalCytokine
    Volume111
    DOIs
    StatePublished - Nov 2018

    Keywords

    • AIDS
    • Baboon
    • CCR5
    • Chemokine
    • Cytokine

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Biochemistry
    • Hematology
    • Molecular Biology

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