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Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation.
Colonna, Lucrezia; Peterson, Christopher W; Schell, John B; Carlson, Judith M; Tkachev, Victor; Brown, Melanie; Yu, Alison; Reddy, Sowmya; Obenza, Willi M; Nelson, Veronica; Polacino, Patricia S; Mack, Heather; Hu, Shiu-Lok; Zeleski, Katie; Hoffman, Michelle; Olvera, Joe; Furlan, Scott N; Zheng, Hengqi; Taraseviciute, Agne; Hunt, Daniel J; Betz, Kayla; Lane, Jennifer F; Vogel, Keith; Hotchkiss, Charlotte E; Moats, Cassie; Baldessari, Audrey; Murnane, Robert D; English, Christopher; Astley, Cliff A; Wangari, Solomon; Agricola, Brian; Ahrens, Joel; Iwayama, Naoto; May, Andrew; Stensland, Laurence; Huang, Meei-Li W; Jerome, Keith R; Kiem, Hans-Peter; Kean, Leslie S.
Afiliação
  • Colonna L; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Peterson CW; Department of Pediatrics, University of Washington, Box 356320, 1959 NE Pacific Street, Seattle, WA, 98195-6320, USA.
  • Schell JB; Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, 98109, WA, USA.
  • Carlson JM; Department of Medicine, University of Washington, Box 356420, 1959 NE Pacific Street, Seattle, WA, 98195-6420, USA.
  • Tkachev V; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Brown M; Vaccine and Gene Therapy Institute, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA.
  • Yu A; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Reddy S; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Obenza WM; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Nelson V; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Polacino PS; Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, 98109, WA, USA.
  • Mack H; Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, 98109, WA, USA.
  • Hu SL; Stem Cell and Gene Therapy Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, 98109, WA, USA.
  • Zeleski K; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Hoffman M; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Olvera J; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Furlan SN; Department of Pharmaceutics, University of Washington, Box 357610, 1959 NE Pacific Street, Seattle, WA, 98195-7610, USA.
  • Zheng H; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Taraseviciute A; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Hunt DJ; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Betz K; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Lane JF; Department of Pediatrics, University of Washington, Box 356320, 1959 NE Pacific Street, Seattle, WA, 98195-6320, USA.
  • Vogel K; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Hotchkiss CE; Department of Pediatrics, University of Washington, Box 356320, 1959 NE Pacific Street, Seattle, WA, 98195-6320, USA.
  • Moats C; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Baldessari A; Department of Pediatrics, University of Washington, Box 356320, 1959 NE Pacific Street, Seattle, WA, 98195-6320, USA.
  • Murnane RD; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • English C; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, 1100 Olive Way, Suite 100, Seattle, WA, 98101, USA.
  • Astley CA; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Wangari S; Montana State University, 100 ARC Bldg. Tietz Hall, Montana State University, P.O. Box 173640, Bozeman, MT, 59717, USA.
  • Agricola B; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Ahrens J; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Iwayama N; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • May A; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Stensland L; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Huang MW; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Jerome KR; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Kiem HP; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
  • Kean LS; Washington National Primate Research Center, 1705 NE Pacific Street, Box 357330, Seattle, WA, 98195, USA.
Nat Commun ; 9(1): 4438, 2018 10 25.
Article em En | MEDLINE | ID: mdl-30361514
ABSTRACT
Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reservatórios de Doenças / Vírus da Imunodeficiência Símia / Transplante de Células-Tronco Hematopoéticas / Transplante Haploidêntico / Complexo Principal de Histocompatibilidade Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reservatórios de Doenças / Vírus da Imunodeficiência Símia / Transplante de Células-Tronco Hematopoéticas / Transplante Haploidêntico / Complexo Principal de Histocompatibilidade Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos