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Magnitude and quality of cytokine and chemokine storm during acute infection distinguish non-progressive and progressive simian immunodeficiency virus infections of nonhuman primates.

Magnitude and quality of cytokine and chemokine storm during acute infection distinguish non-progressive and progressive simian immunodeficiency virus infections of nonhuman primates.
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Keating SM, Heitman JW, Wu S, Deng X, Stacey AR, Zahn RC, de la Rosa M, Finstad SL, Lifson JD, Piatak M, Gauduin MC, Kessler BM, Ternette N, Carville A, Johnson RP, Desrosiers RC, Letvin NL, Borrow P, Norris PJ, Schmitz JE,


Keating SM, Heitman JW, Wu S, Deng X, Stacey AR, Zahn RC, de la Rosa M, Finstad SL, Lifson JD, Piatak M, Gauduin MC, Kessler BM, Ternette N, Carville A, Johnson RP, Desrosiers RC, Letvin NL, Borrow P, Norris PJ, Schmitz JE, (click to view)

Keating SM, Heitman JW, Wu S, Deng X, Stacey AR, Zahn RC, de la Rosa M, Finstad SL, Lifson JD, Piatak M, Gauduin MC, Kessler BM, Ternette N, Carville A, Johnson RP, Desrosiers RC, Letvin NL, Borrow P, Norris PJ, Schmitz JE,

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Journal of virology 2016 9 14() pii

Abstract

Acute HIV infection represents a period of intense immune perturbation and activation of the host immune system. Study of the eclipse and viral expansion phases of infection is difficult in humans, but studies in non-progressive and progressive nonhuman primate infection models can provide significant insight into critical events occurring during this time. Cytokines, chemokines and other soluble immune factors were measured in longitudinal samples from rhesus macaques infected with either SIVmac251 (progressive infection) or SIVmac239Δnef (attenuated/non-progressive infection), and from African green monkeys infected with SIVsab9315BR (non-pathogenic infection). Levels of acute-phase peak viral replication were highest in SIVmac251 infection, but correlated positively with viremia at three months post-infection in all three infection models. SIVmac251 infection was associated with stronger corresponding acute-phase cytokine/chemokine responses than the non-progressive infections. Production of IL-15, IL-18, IFN-γ, G-CSF, MCP-1, MIP-1β and SAA during acute SIVmac251 infection, but not SIVmac239Δnef or SIVsab9315BR infection, correlated positively with chronic viremia at three months post infection. Acute-phase production of MCP-1 correlated with viremia at three months post infection in both non-progressive infections. Finally, a positive correlation between the acute-phase area under the curve (AUC) IL-6 and sCD40L and chronic viremia was only observed in the non-progressive infections models. While we observed dynamic acute inflammatory immune responses in both progressive and non-progressive SIV infections, the responses in the non-progressive infections were not only lower in magnitude but also qualitatively different biomarkers of disease progression.

IMPORTANCE
NHP models of HIV infection constitute a powerful tool to study viral pathogenesis to gain critical information for a better understanding of HIV infection in humans. Here, we studied progressive and non-progressive SIV infection models in both natural and non-natural host NHP species. Regardless of the pathogenicity of the virus infection or NHP species studied, the magnitude of viremia, as measured by area under the curve during the first 4 weeks of infection, positively correlated with viremia in chronic infection. The magnitude of cytokine and chemokine responses during primary infection also correlated positively with both acute-phase and chronic viremia. However, the pattern and levels of specific cytokines and chemokines produced differed between non-progressive and progressive SIV infection models. The qualitative differences in the early immune response in progressive and non-progressive infections identified here correlate with and may provide insights into the basis of differences in the subsequent course of disease.

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