title: Inhibition of adaptive immune responses leads to a fatal clinical outcome in SIV-infected pigtailed macaques but not vervet African green monkeys.
abstract: African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIV(agmVer90) to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. jschmitz@bidmc.harvard.edu
authors.forename: Jörn E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: Roland C
authors.initials: RC
authors.lastname: Zahn
authors.forename: Charles R
authors.initials: CR
authors.lastname: Brown
authors.forename: Melisa D
authors.initials: MD
authors.lastname: Rett
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Haili
authors.initials: H
authors.lastname: Tang
authors.forename: Sarah
authors.initials: S
authors.lastname: Pryputniewicz
authors.forename: Russell A
authors.initials: RA
authors.lastname: Byrum
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Allan
authors.forename: Simoy
authors.initials: S
authors.lastname: Goldstein
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops / Q000276:immunology* / Q000821:virology; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008212:Lymphocyte Depletion; D008254:Macaca nemestrina / Q000276:immunology* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014766:Viremia
chemical_list: D018951:Antigens, CD20