TY - JOUR
T1 - Magnitude and quality of cytokine and chemokine storm during acute infection distinguish nonprogressive and progressive simian immunodeficiency virus infections of nonhuman primates
AU - Keating, Sheila M.
AU - Heitman, John W.
AU - Wu, Shiquan
AU - Deng, Xutao
AU - Stacey, Andrea R.
AU - Zahn, Roland C.
AU - de la Rosa, Maurus
AU - Finstad, Samantha L.
AU - Lifson, Jeffrey D.
AU - Piatak, Michael
AU - Gauduin, Marie Claire
AU - Kessler, Benedikt M.
AU - Ternette, Nicola
AU - Carville, Angela
AU - Johnson, R. Paul
AU - Desrosiers, Ronald C.
AU - Letvin, Norman L.
AU - Borrow, Persephone
AU - Norris, Philip J.
AU - Schmitz, Joern E.
N1 - Funding Information:
This work was supported by NIH, NIAID, Division of AIDS, grants AI0678501 (CHAVI, Center for HIV AIDS Vaccine Immunology) (B.M.K., P.B., N.L.L., P.J.N., J.E.S.) and AI065335 (J.E.S.) and in part with federal funds from the NCI/NIH under contract HHSN261200800001E. This publication was made possible with help from the Harvard University Center for AIDS Research (CFAR), an NIH-funded program (P30-AI060354), which is supported by the following NIH cofunding and participating institutes and centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NIDDK, NIGMS, FIC, and OAR. P.B. is a Jenner Institute Investigator. This work, including the efforts of Sheila M. Keating, John W. Heitman, Shiquan Wu, Xutao Deng, Andrea R. Stacey, Roland C. Zahn, Maurus de la Rosa, Samantha L. Finstad, Jeffrey D. Lifson, Michael Piatak, Jr., Benedikt M. Kessler, Nicola Ternette, Angela Carville, R. Paul Johnson, Ronald C. Desrosiers, Norman L. Letvin, Persephone Borrow, Philip J. Norris, and Joern E. Schmitz, was funded by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (AI0678501 and AI065335). This work, including the efforts of Roland C. Zahn, Maurus de la Rosa, Samantha L. Finstad, and Joern E. Schmitz, was funded by Harvard University Center for AIDS Research (HU CFAR) (P30-AI060354).
Publisher Copyright:
© 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016
Y1 - 2016
N2 - Acute human immunodeficiency virus (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 nonprogressive and progressive nonhuman primate (NHP) 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/nonprogressive infection) and from African green monkeys infected with SIVsab9315BR (nonpathogenic infection). Levels of acute-phase peak viral replication were highest in SIVmac251 infection but correlated positively with viremia at 3 months postinfection in all three infection models. SIVmac251 infection was associated with stronger corresponding acute-phase cytokine/chemokine responses than the nonprogressive infections. The production of interleukin 15 (IL-15), IL-18, gamma interferon (IFN-γ), granulocyte colony- stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP- 1β), and serum amyloid A protein (SAA) during acute SIVmac251 infection, but not during SIVmac239Δnef or SIVsab9315BR infection, correlated positively with chronic viremia at 3 months postinfection. Acute-phase production of MCP-1 correlated with viremia at 3 months postinfection in both nonprogressive infections. Finally, a positive correlation between the acute-phase area under the curve (AUC) for IL-6 and soluble CD40 ligand (sCD40L) and chronic viremia was observed only for the nonprogressive infection models. While we observed dynamic acute inflammatory immune responses in both progressive and nonprogressive SIV infections, the responses in the nonprogressive infections were not only lower in magnitude but also qualitatively different biomarkers of disease progression.
AB - Acute human immunodeficiency virus (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 nonprogressive and progressive nonhuman primate (NHP) 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/nonprogressive infection) and from African green monkeys infected with SIVsab9315BR (nonpathogenic infection). Levels of acute-phase peak viral replication were highest in SIVmac251 infection but correlated positively with viremia at 3 months postinfection in all three infection models. SIVmac251 infection was associated with stronger corresponding acute-phase cytokine/chemokine responses than the nonprogressive infections. The production of interleukin 15 (IL-15), IL-18, gamma interferon (IFN-γ), granulocyte colony- stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP- 1β), and serum amyloid A protein (SAA) during acute SIVmac251 infection, but not during SIVmac239Δnef or SIVsab9315BR infection, correlated positively with chronic viremia at 3 months postinfection. Acute-phase production of MCP-1 correlated with viremia at 3 months postinfection in both nonprogressive infections. Finally, a positive correlation between the acute-phase area under the curve (AUC) for IL-6 and soluble CD40 ligand (sCD40L) and chronic viremia was observed only for the nonprogressive infection models. While we observed dynamic acute inflammatory immune responses in both progressive and nonprogressive SIV infections, the responses in the nonprogressive infections were not only lower in magnitude but also qualitatively different biomarkers of disease progression.
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U2 - 10.1128/JVI.01061-16
DO - 10.1128/JVI.01061-16
M3 - Article
C2 - 27630228
AN - SCOPUS:84995511362
VL - 90
SP - 10339
EP - 10350
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 22
ER -