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Title: Experimental depletion of CD8+ cells in acutely SIVagm-Infected African Green Monkeys results in increased viral replication

Journal Article · · Retrovirology
 [1];  [2];  [3];  [4];  [3];  [5];  [6]
  1. Tulane National Primate Research Center, Covington LA (United States). Division of Microbiology; DOE/OSTI
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Tulane National Primate Research Center, Covington LA (United States). Division of Microbiology
  4. Tulane National Primate Research Center, Covington LA (United States). Division of Veterinary Sciences
  5. Tulane National Primate Research Center, Covington LA (United States). Division of Microbiology; Univ. of Pittsburgh, PA (United States)
  6. Tulane National Primate Research Center, Covington LA (United States). Division of Comparative Pathology; Univ. of Pittsburgh, PA (United States)
+ Show Author Affiliations

Background: In vivo CD8+ cell depletions in pathogenic SIV infections identified a key role for cellular immunity in controlling viral load (VL) and disease progression. However, similar studies gave discordant results in chronicallyinfected SMs, leading some authors to propose that in natural hosts, SIV replication is independent of cellular immunity. To assess the role of cellular immune responses in the control of SIV replication in natural hosts, we investigated the impact of CD8+ cell depletion during acute SIV infection in AGMs. Results: Nine AGMs were infected with SIVagm.sab and were followed up to day 225 p.i. Four were intravenously infused with the cM-T807 antibody on days 0 (50 mg/kg), 6, and 13 (10 mg/kg, respectively) post infection (p.i.). CD8+ cells were depleted for up to 28 days p.i. in peripheral blood and LNs in all treated AGMs. Partial CD8+ T cell depletion occurred in the intestine. SIVagm VLs peaked at similar levels in both groups (107-108 RNA copies/ml). However, while VLs were controlled in undepleted AGMs, reaching set-point levels (104-105 RNA copies/ml) by day 28 p.i., high VLs (>106 RNA copies/ml) were maintained by day 21 p.i. in CD8-depleted AGMs. By day 42 p.i., VLs were comparable between the two groups. The levels of immune activation and proliferation remained elevated up to day 72 p.i. in CD8-depleted AGMs and returned to preinfection levels in controls by day 28 p.i. None of the CD8-depleted animals progressed to AIDS. Conclusion: CD8+ cells are responsible for a partial control of postacute viral replication in SIVagm.sab-infected AGMs. In contrast to macaques, the SIVagm-infected AGMs are able to control viral replication after recovery of the CD8+ T cells and avoid disease progression.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
National Institute of Allergy and Infectious Diseases (NIAID); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1626607
Journal Information:
Retrovirology, Journal Name: Retrovirology Journal Issue: 1 Vol. 7; ISSN 1742-4690
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro. journal July 1998
HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells journal June 2006
The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus journal July 2006
Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts journal September 2006
Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain journal April 2009
Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease journal April 2010
Inhibition of Adaptive Immune Responses Leads to a Fatal Clinical Outcome in SIV-Infected Pigtailed Macaques but Not Vervet African Green Monkeys journal December 2009
Identification of Multiple Simian Immunodeficiency Virus (SIV)-Specific CTL Epitopes in Sooty Mangabeys with Natural and Experimentally Acquired SIV Infection journal January 2000
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A Nonhuman Primate Model for the Selective Elimination of CD8+ Lymphocytes Using a Mouse-Human Chimeric Monoclonal Antibody journal June 1999
Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts journal September 2008
High levels of SIVmnd-1 replication in chronically infected Mandrillus sphinx journal December 2003
Studies using a viral challenge and CD8 T cell depletions on the roles of cellular and humoral immunity in the control of an SHIV-89.6P challenge in DNA/MVA-vaccinated macaques journal December 2005
Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: Role of SIV-specific CD8+ T cell responses journal September 2006
Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics. journal April 1995
Dramatic Rise in Plasma Viremia after CD8 + T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques journal March 1999
Effects of in Vivo Cd8 + T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine journal June 1999
Profound CD4 + /CCR5 + T cell expansion is induced by CD8 + lymphocyte depletion but does not account for accelerated SIV pathogenesis journal June 2009
Synthetic Peptide Strategy for the Detection of and Discrimination among Highly Divergent Primate Lentiviruses journal July 2001
Chronic SIV infection ultimately causes immunodeficiency in African non-human primates journal January 2001
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Use of an anti-CD16 antibody for in vivo depletion of natural killer cells in rhesus macaques journal June 2008
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Simian Immunodeficiency Virus SIVrcm, a Unique CCR2-Tropic Virus, Selectively Depletes Memory CD4+ T Cells in Pigtailed Macaques through Expanded Coreceptor Usage In Vivo journal June 2009
Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host journal August 2009
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Mamu-B*08-Positive Macaques Control Simian Immunodeficiency Virus Replication journal May 2007
With Minimal Systemic T-Cell Expansion, CD8 + T Cells Mediate Protection of Rhesus Macaques Immunized with Attenuated Simian-Human Immunodeficiency Virus SHIV89.6 from Vaginal Challenge with Simian Immunodeficiency Virus journal November 2008
Differential CD4 + T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection journal January 2009
Simian Immunodeficiency Virus (SIV)-Specific CD8 + T-Cell Responses in Vervet African Green Monkeys Chronically Infected with SIVagm journal December 2008
Gag p27-Specific B- and T-Cell Responses in Simian Immunodeficiency Virus SIVagm-Infected African Green Monkeys journal March 2009
In Vivo Natural Killer Cell Depletion during Primary Simian Immunodeficiency Virus Infection in Rhesus Monkeys journal July 2008
Subdominant CD8+ T-Cell Responses Are Involved in Durable Control of AIDS Virus Replication journal January 2007
Simian Immunodeficiency Virus SIVagm Dynamics in African Green Monkeys journal January 2008
Paucity of CD4 + CCR5 + T Cells May Prevent Transmission of Simian Immunodeficiency Virus in Natural Nonhuman Primate Hosts by Breast-Feeding journal June 2008
Increased Loss of CCR5+ CD45RA- CD4+ T Cells in CD8+ Lymphocyte-Depleted Simian Immunodeficiency Virus-Infected Rhesus Monkeys journal March 2008
Administration of an Anti-CD8 Monoclonal Antibody Interferes with the Clearance of Chimeric Simian/Human Immunodeficiency Virus during Primary Infections of Rhesus Macaques journal January 1998
Normal T-Cell Turnover in Sooty Mangabeys Harboring Active Simian Immunodeficiency Virus Infection journal February 2000
Cytokine Expression, Natural Killer Cell Activation, and Phenotypic Changes in Lymphoid Cells from Rhesus Macaques during Acute Infection with Pathogenic Simian Immunodeficiency Virus journal February 2000
Role of CD8+ Lymphocytes in Control of Simian Immunodeficiency Virus Infection and Resistance to Rechallenge after Transient Early Antiretroviral Treatment journal November 2001
High Levels of Viral Replication Contrast with Only Transient Changes in CD4 + and CD8 + Cell Numbers during the Early Phase of Experimental Infection with Simian Immunodeficiency Virus SIVmnd-1 in Mandrillus sphinx journal October 2002
Direct Relationship between Suppression of Virus-Specific Immunity and Emergence of Cytomegalovirus Disease in Simian AIDS journal May 2003
Control of Viremia and Prevention of Simian-Human Immunodeficiency Virus-Induced Disease in Rhesus Macaques Immunized with Recombinant Vaccinia Viruses plus Inactivated Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Particles journal January 2003
CD8+-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment journal April 2004
Impact of Viral Factors on Very Early In Vivo Replication Profiles in Simian Immunodeficiency Virus SIVagm-Infected African Green Monkeys journal May 2005
Divergent Host Responses during Primary Simian Immunodeficiency Virus SIVsm Infection of Natural Sooty Mangabey and Nonnatural Rhesus Macaque Hosts journal April 2005
Simian Immunodeficiency Virus SIVagm.sab Infection of Caribbean African Green Monkeys: a New Model for the Study of SIV Pathogenesis in Natural Hosts journal April 2006
The High-Frequency Major Histocompatibility Complex Class I Allele Mamu-B*17 Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 Replication journal May 2006
Th-1-Type Cytotoxic CD8 + T-Lymphocyte Responses to Simian Immunodeficiency Virus (SIV) Are a Consistent Feature of Natural SIV Infection in Sooty Mangabeys journal March 2006
Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills ( Mandrillus sphinx ) journal April 2006
High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. journal January 1995
Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro. journal July 1998
HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells journal June 2006
The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus journal July 2006
Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts journal September 2006
Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain journal April 2009
Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease journal April 2010
Inhibition of Adaptive Immune Responses Leads to a Fatal Clinical Outcome in SIV-Infected Pigtailed Macaques but Not Vervet African Green Monkeys journal December 2009
Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys journal December 2009
Emergence of CTL Coincides with Clearance of Virus During Primary Simian Immunodeficiency Virus Infection in Rhesus Monkeys journal May 1999
Identification of Multiple Simian Immunodeficiency Virus (SIV)-Specific CTL Epitopes in Sooty Mangabeys with Natural and Experimentally Acquired SIV Infection journal January 2000
Depletion of CD8 + Cells in Sooty Mangabey Monkeys Naturally Infected with Simian Immunodeficiency Virus Reveals Limited Role for Immune Control of Virus Replication in a Natural Host Species journal June 2007
Acute Loss of Intestinal CD4 + T Cells Is Not Predictive of Simian Immunodeficiency Virus Virulence journal August 2007
Cutting Edge: Experimentally Induced Immune Activation in Natural Hosts of Simian Immunodeficiency Virus Induces Significant Increases in Viral Replication and CD4 + T Cell Depletion journal November 2008

Cited By (18)

Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys journal October 2017
Factors Associated with Siman Immunodeficiency Virus Transmission in a Natural African Nonhuman Primate Host in the Wild journal March 2014
Immuno-epidemiological Modeling of HIV-1 Predicts High Heritability of the Set-Point Virus Load, while Selection for CTL Escape Dominates Virulence Evolution journal December 2014
SIVagm Infection in Wild African Green Monkeys from South Africa: Epidemiology, Natural History, and Evolutionary Considerations journal January 2013
Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques journal January 2016
Lymph Node Cellular and Viral Dynamics in Natural Hosts and Impact for HIV Cure Strategies journal April 2018
Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys journal October 2017
The dynamics of simian immunodeficiency virus after depletion of CD8+ cells journal August 2018
Pathogenic Correlates of Simian Immunodeficiency Virus-Associated B Cell Dysfunction journal December 2017
Critical Role for the Adenosine Pathway in Controlling Simian Immunodeficiency Virus-Related Immune Activation and Inflammation in Gut Mucosal Tissues journal July 2015
Dynamics of Simian Immunodeficiency Virus Two-Long-Terminal-Repeat Circles in the Presence and Absence of CD8 + Cells journal April 2018
Factors Associated with Siman Immunodeficiency Virus Transmission in a Natural African Nonhuman Primate Host in the Wild journal March 2014
Pathogenic Features Associated with Increased Virulence upon Simian Immunodeficiency Virus Cross-Species Transmission from Natural Hosts journal April 2014
Immunovirological Analyses of Chronically Simian Immunodeficiency Virus SIVmnd-1- and SIVmnd-2-Infected Mandrills (Mandrillus sphinx) journal September 2011
Immunovirological Analyses of Chronically Simian Immunodeficiency Virus SIVmnd-1- and SIVmnd-2-Infected Mandrills (Mandrillus sphinx) journal January 2012
Mucosal Simian Immunodeficiency Virus Transmission in African Green Monkeys: Susceptibility to Infection Is Proportional to Target Cell Availability at Mucosal Sites journal February 2012
SIVagm Infection in Wild African Green Monkeys from South Africa: Epidemiology, Natural History, and Evolutionary Considerations journal January 2013
Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques journal January 2016

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59 BASIC BIOLOGICAL SCIENCES
Cell Depletion
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Natural Host
Preinfection Level
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