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CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells

Journal Article · · PLoS Pathogens
 [1];  [2];  [3];  [3];  [3];  [4];  [5];  [4];  [6];  [7];  [8];  [7];  [2];  [2];  [9]
  1. Univ. of Pennsylvania, Philadelphia, PA (United States). Dept. of Pathology and Lab. Medicine; Emory Univ., Atlanta, GA (United States). Yerkes National Primate Research Center; DOE/OSTI
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
  3. Univ. of Pennsylvania, Philadelphia, PA (United States). Dept. of Pathology and Lab. Medicine
  4. Emory Univ., Atlanta, GA (United States). Yerkes National Primate Research Center
  5. Gilead Sciences, Inc., Foster City, CA (United States)
  6. National Cancer Institute, Bethesda, MD (United States). Science Applications International Corporation-Frederick, Inc. AIDS and Cancer Virus Program
  7. Harvard Medical School, Boston, MA (United States). Beth Israel Deaconess Medical Center
  8. Tulane Univ., New Orleans, LA (United States). Tulane Health Sciences Center. Tulane national primate Research Center
  9. Univ. of Pennsylvania, Philadelphia, PA (United States). Dept. of Pathology and Lab. Medicine; Emory Univ., Atlanta, GA (United States). Yerkes National Primate Research Center
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While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.

Research Organization:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1627895
Journal Information:
PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 1 Vol. 6; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (38)

Innate immune recognition and activation during HIV infection journal June 2010
HIV Replication Is Not Controlled by CD8+ T Cells during the Acute Phase of the Infection in Humanized Mice journal September 2015
Noncytolytic CD8+ Cell Mediated Antiviral Response Represents a Strong Element in the Immune Response of Simian Immunodeficiency Virus-Infected Long-Term Non-Progressing Rhesus Macaques journal November 2015
Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa journal January 2017
Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection journal August 2016
Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques journal December 2016
Long-term surviving influenza infected cells evade CD8+ T cell mediated clearance journal September 2019
Do HIV-specific CTL continue to have an antiviral function during antiretroviral therapy? If not, why not, and what can be done about it? journal January 2013
Quantification of viral infection dynamics in animal experiments journal January 2013
Special Issue “Mathematical Modeling of Viral Infections” journal June 2018
Mechanisms of CD8 + T cell-mediated suppression of HIV/SIV replication journal March 2018
Characterization of a canine homolog of hepatitis C virus journal May 2011
Activated CD4 + CCR5 + T cells in the rectum predict increased SIV acquisition in SIVGag/Tat-vaccinated rhesus macaques journal December 2014
Impaired immune evasion in HIV through intracellular delays and multiple infection of cells journal April 2012
T-cell subset differentiation and antibody responses following antiretroviral therapy during simian immunodeficiency virus infection journal August 2018
Immune activation and HIV persistence: implications for curative approaches to HIV infection journal June 2013
Mucosal immunology of HIV infection journal June 2013
The dynamics of simian immunodeficiency virus after depletion of CD8+ cells journal August 2018
Delayed differentiation of potent effector CD8 + T cells reducing viremia and reservoir seeding in acute HIV infection journal February 2017
Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8 + T cells journal December 2019
Initial HIV-1 Antigen-Specific CD8+ T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication journal April 2012
Differential Impact of In Vivo CD8 + T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques journal June 2015
Immunological and Virological Analyses of Rhesus Macaques Immunized with Chimpanzee Adenoviruses Expressing the Simian Immunodeficiency Virus Gag/Tat Fusion Protein and Challenged Intrarectally with Repeated Low Doses of SIVmac journal June 2013
Dynamics of Simian Immunodeficiency Virus Two-Long-Terminal-Repeat Circles in the Presence and Absence of CD8 + Cells journal April 2018
Modeling the within-host dynamics of HIV infection journal September 2013
Quantification of the Relative Importance of CTL, B Cell, NK Cell, and Target Cell Limitation in the Control of Primary SIV-Infection journal March 2011
Implications of CTL-Mediated Killing of HIV-Infected Cells during the Non-Productive Stage of Infection journal February 2011
Can Non-lytic CD8+ T Cells Drive HIV-1 Escape? journal November 2013
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CD8+ lymphocyte control of SIV infection during antiretroviral therapy journal October 2018
Thymosin α 1 potentiates the release by CD8 + cells of soluble factors able to inhibit HIV-1 and human T lymphotropic virus 1 infection in vitro journal June 2015
Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection
  • Jean-Pierre, Routy,; J., McMichael, Andrew; Sorachai, Nitayaphan,
  • The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/fh7w-ks33
text January 2016
Initial HIV-1 Antigen-Specific CD8+ T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication text January 2012
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Implications of CTL-Mediated Killing of HIV-Infected Cells during the Non-Productive Stage of Infection text January 2011

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