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Journal of Virology, October 2009, p. 10347-10357, Vol. 83, No. 20
0022-538X/09/$08.00+0 doi:10.1128/JVI.00880-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host
,
Thaidra Gaufin,1
Melissa Pattison,1
Rajeev Gautam,1
Crystal Stoulig,2
Jason Dufour,3
Jeanne MacFarland,1
Daniel Mandell,1
Coty Tatum,1
Matthew H. Marx,2
Ruy M. Ribeiro,4
David Montefiori,5
Cristian Apetrei,1,6,8 and
Ivona Pandrea2,7,8*
Divisions of Microbiology,1 Comparative Pathology,2 Veterinary Medicine, Tulane National Primate Research Center, Covington, Louisiana 70433,3 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 87545,4 Department of Surgery, Duke University, Durham, North Carolina 27710,5 Department of Tropical Medicine, School of Public Health, Tulane University, New Orleans, Louisiana 70112,6 Department of Pathology, School of Medicine, Tulane University, New Orleans, Louisiana 70112,7 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania 152618
Received 1 May 2009/ Accepted 30 July 2009
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 107 to 108 copies/ml; set-point values were 104 to 105 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.
* Corresponding author. Mailing address: Center for Vaccine Research, University of Pittsburgh, 9045 Biomedial Science Tower 3, 3501 Fifth Ave., Pittsburgh, PA15261. Phone: (412) 624-4480. Fax: (412) 624-4440. E-mail: pandrea{at}pitt.edu
Published ahead of print on 5 August 2009.
Supplemental material for this article may be found at http://jvi.asm.org/.
Journal of Virology, October 2009, p. 10347-10357, Vol. 83, No. 20
0022-538X/09/$08.00+0 doi:10.1128/JVI.00880-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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