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Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.
Wu, Helen L; Busman-Sahay, Kathleen; Weber, Whitney C; Waytashek, Courtney M; Boyle, Carla D; Bateman, Katherine B; Reed, Jason S; Hwang, Joseph M; Shriver-Munsch, Christine; Swanson, Tonya; Northrup, Mina; Armantrout, Kimberly; Price, Heidi; Robertson-LeVay, Mitch; Uttke, Samantha; Kumar, Mithra R; Fray, Emily J; Taylor-Brill, Sol; Bondoc, Stephen; Agnor, Rebecca; Junell, Stephanie L; Legasse, Alfred W; Moats, Cassandra; Bochart, Rachele M; Sciurba, Joseph; Bimber, Benjamin N; Sullivan, Michelle N; Dozier, Brandy; MacAllister, Rhonda P; Hobbs, Theodore R; Martin, Lauren D; Panoskaltsis-Mortari, Angela; Colgin, Lois M A; Siliciano, Robert F; Siliciano, Janet D; Estes, Jacob D; Smedley, Jeremy V; Axthelm, Michael K; Meyers, Gabrielle; Maziarz, Richard T; Burwitz, Benjamin J; Stanton, Jeffrey J; Sacha, Jonah B.
Afiliação
  • Wu HL; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Busman-Sahay K; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Weber WC; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Waytashek CM; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Boyle CD; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Bateman KB; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Reed JS; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Hwang JM; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Shriver-Munsch C; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Swanson T; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Northrup M; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Armantrout K; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Price H; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Robertson-LeVay M; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Uttke S; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Kumar MR; Department of Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
  • Fray EJ; Department of Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
  • Taylor-Brill S; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Bondoc S; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Agnor R; Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Junell SL; Division of Medical Physics, Department of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Legasse AW; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Moats C; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Bochart RM; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Sciurba J; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Bimber BN; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Sullivan MN; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Dozier B; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • MacAllister RP; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Hobbs TR; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Martin LD; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Panoskaltsis-Mortari A; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55454, USA.
  • Colgin LMA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Siliciano RF; Department of Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
  • Siliciano JD; Department of Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
  • Estes JD; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Smedley JV; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Axthelm MK; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Meyers G; Division of Blood and Marrow Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Maziarz RT; Division of Blood and Marrow Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Burwitz BJ; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Stanton JJ; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA.
  • Sacha JB; Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97007, USA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97007, USA. Electronic address: sacha@ohsu.edu.
Immunity ; 56(7): 1649-1663.e5, 2023 07 11.
Article em En | MEDLINE | ID: mdl-37236188
ABSTRACT
Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5Δ32/Δ32) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV+, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4+ T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / Síndrome de Imunodeficiência Adquirida dos Símios / Vírus da Imunodeficiência Símia / Transplante de Células-Tronco Hematopoéticas Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por HIV / Síndrome de Imunodeficiência Adquirida dos Símios / Vírus da Imunodeficiência Símia / Transplante de Células-Tronco Hematopoéticas Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos