title: Antiviral antibodies are necessary for control of simian immunodeficiency virus replication.
abstract: To better define the role of B cells in the control of pathogenic simian immunodeficiency virus (SIV) replication, six rhesus monkeys were depleted of B cells by intravenous infusion of rituximab (anti-CD20) 28 days and 7 days before intravaginal SIVmac239 inoculation and every 21 days thereafter until AIDS developed. Although the blood and tissues were similarly depleted of B cells, anti-SIV immunoglobulin G (IgG) antibody responses were completely blocked in only three of the six animals. In all six animals, levels of viral RNA (vRNA) in plasma peaked at 2 weeks and declined by 4 weeks postinoculation (PI). However, the three animals prevented from making an anti-SIV antibody response had significantly higher plasma vRNA levels through 12 weeks PI (P = 0.012). The remaining three B-cell-depleted animals made moderate anti-SIV IgG antibody responses, maintained moderate plasma SIV loads, and showed an expected rate of disease progression, surviving to 24 weeks PI without developing AIDS. In contrast, all three of the B-cell-depleted animals prevented from making anti-SIV IgG responses developed AIDS by 16 weeks PI (P = 0.0001). These observations indicate that antiviral antibody responses are critical in maintaining effective control of SIV replication at early time points postinfection.
authors.affiliation: Center for Comparative Medicine, California National Primate Research Center, University of California, Davis, Davis, California 95616, USA. cjmiller@ucdavis.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.forename: Meritxell
authors.initials: M
authors.lastname: Genescà
authors.forename: Kristina
authors.initials: K
authors.lastname: Abel
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Donald
authors.initials: D
authors.lastname: Forthal
authors.forename: Kristen
authors.initials: K
authors.lastname: Bost
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Favre
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000097:blood; D017452:Receptors, IgG / Q000235:genetics; D000069283:Rituximab; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007155:Immunologic Factors; D012367:RNA, Viral; D017452:Receptors, IgG; D000069283:Rituximab