title: B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.
abstract: Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukazawa
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Lum
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Afam A
authors.initials: AA
authors.lastname: Okoye
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Haesun
authors.initials: H
authors.lastname: Park
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kenta
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Bae
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Shoko I
authors.initials: SI
authors.lastname: Hagen
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shoemaker
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Deleage
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors.forename: Carissa
authors.initials: C
authors.lastname: Lucero
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors.forename: David
authors.initials: D
authors.lastname: Morcock
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Tonya
authors.initials: T
authors.lastname: Swanson
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Legasse
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.affiliation: Gilead Sciences, Inc., Foster City, California, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hesselgesser
authors.affiliation: Gilead Sciences, Inc., Foster City, California, USA.
authors.forename: Romas
authors.initials: R
authors.lastname: Geleziunas
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: 1] Vaccine and Gene Therapy Institute, Oregon Health &Science University, Beaverton, Oregon, USA. [2] Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D019562:Viral Load; D014779:Virus Replication