Effect of B-cell depletion on viral replication and clinical outcome of simian immunodeficiency virus infection in a natural host.
Simian immunodeficiency virus (SIV)-infected African nonhuman primates do not progress to AIDS in spite of high and persistent viral loads (VLs). Some authors consider the high viral replication observed in chronic natural SIV infections to be due to lower anti-SIV antibody titers than those in rhesus macaques, suggesting a role of antibodies in controlling viral replication. We therefore investigated the impact of antibody responses on the outcome of acute and chronic SIVagm replication in African green monkeys (AGMs). Nine AGMs were infected with SIVagm.sab. Four AGMs were infused with 50 mg/kg of body weight anti-CD20 (rituximab; a gift from Genentech) every 21 days, starting from day -7 postinfection up to 184 days. The remaining AGMs were used as controls and received SIVagm only. Rituximab-treated AGMs were successfully depleted of CD20 cells in peripheral blood, lymph nodes (LNs), and intestine, as shown by the dynamics of CD20+ and CD79a+ cells. There was no significant difference in VLs between CD20-depleted AGMs and control monkeys: peak VLs ranged from 10(7) to 10(8) copies/ml; set-point values were 10(4) to 10(5) SIV RNA copies/ml. Levels of acute mucosal CD4+ T-cell depletion were similar for treated and nontreated animals. SIVagm seroconversion was delayed for the CD20-depleted AGMs compared to results for the controls. There was a significant difference in both the timing and magnitude of neutralizing antibody responses for CD20-depleted AGMs compared to results for controls. CD20 depletion significantly altered the histological structure of the germinal centers in the LNs and Peyer's patches. Our results, although obtained with a limited number of animals, suggest that humoral immune responses play only a minor role in the control of SIV viral replication during acute and chronic SIV infection in natural hosts.
Gaufin
Thaidra
T
Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
Pattison
Melissa
M
Gautam
Rajeev
R
Stoulig
Crystal
C
Dufour
Jason
J
MacFarland
Jeanne
J
Mandell
Daniel
D
Tatum
Coty
C
Marx
Matthew H
MH
Ribeiro
Ruy M
RM
Montefiori
David
D
Apetrei
Cristian
C
Pandrea
Ivona
I
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D005434:Flow Cytometry; D007155:Immunologic Factors / Q000008:administration & dosage; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008992:Monkey Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000069283:Rituximab; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D018951:Antigens, CD20; D007155:Immunologic Factors; D000069283:Rituximab