title: Low levels of SIV infection in sooty mangabey central memory CD⁴⁺ T cells are associated with limited CCR5 expression.
abstract: Naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys do not progress to AIDS despite high-level virus replication. We previously showed that the fraction of CD4(+)CCR5(+) T cells is lower in sooty mangabeys compared to humans and macaques. Here we found that, after in vitro stimulation, sooty mangabey CD4(+) T cells fail to upregulate CCR5 and that this phenomenon is more pronounced in CD4(+) central memory T cells (T(CM) cells). CD4(+) T cell activation was similarly uncoupled from CCR5 expression in sooty mangabeys in vivo during acute SIV infection and the homeostatic proliferation that follows antibody-mediated CD4(+) T cell depletion. Sooty mangabey CD4(+) T(CM) cells that express low amounts of CCR5 showed reduced susceptibility to SIV infection both in vivo and in vitro when compared to CD4(+) T(CM) cells of rhesus macaques. These data suggest that low CCR5 expression on sooty mangabey CD4(+) T cells favors the preservation of CD4(+) T cell homeostasis and promotes an AIDS-free status by protecting CD4(+) T(CM) cells from direct virus infection.
authors.affiliation: Yerkes National Primate Research Center, Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, Georgia, USA. mirko.paiardini@emory.edu
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Barbara
authors.initials: B
authors.lastname: Cervasi
authors.forename: Elane
authors.initials: E
authors.lastname: Reyes-Aviles
authors.forename: Luca
authors.initials: L
authors.lastname: Micci
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ortiz
authors.forename: Ann
authors.initials: A
authors.lastname: Chahroudi
authors.forename: Carol
authors.initials: C
authors.lastname: Vinton
authors.forename: Shari N
authors.initials: SN
authors.lastname: Gordon
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.forename: Nicholas
authors.initials: N
authors.lastname: Francella
authors.forename: Paul L
authors.initials: PL
authors.lastname: Hallberg
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cramer
authors.forename: Timothy
authors.initials: T
authors.lastname: Schlub
authors.forename: Ming Liang
authors.initials: ML
authors.lastname: Chan
authors.forename: Nadeene E
authors.initials: NE
authors.lastname: Riddick
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Collman
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.forename: Ivona
authors.initials: I
authors.lastname: Pandrea
authors.forename: James
authors.initials: J
authors.lastname: Else
authors.forename: Jan
authors.initials: J
authors.lastname: Munch
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D016665:Cercocebus atys / Q000276:immunology; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology; D008297:Male; D019713:Receptors, CCR5 / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load / Q000276:immunology
chemical_list: D019713:Receptors, CCR5