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Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation

Author

Listed:
  • Lucrezia Colonna

    (Seattle Children’s Research Institute
    University of Washington)

  • Christopher W. Peterson

    (Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N
    University of Washington)

  • John B. Schell

    (Seattle Children’s Research Institute
    Vaccine and Gene Therapy Institute)

  • Judith M. Carlson

    (Seattle Children’s Research Institute)

  • Victor Tkachev

    (Seattle Children’s Research Institute)

  • Melanie Brown

    (Seattle Children’s Research Institute)

  • Alison Yu

    (Seattle Children’s Research Institute)

  • Sowmya Reddy

    (Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N)

  • Willi M. Obenza

    (Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N)

  • Veronica Nelson

    (Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N)

  • Patricia S. Polacino

    (Washington National Primate Research Center)

  • Heather Mack

    (Washington National Primate Research Center)

  • Shiu-Lok Hu

    (Washington National Primate Research Center
    University of Washington)

  • Katie Zeleski

    (Seattle Children’s Research Institute)

  • Michelle Hoffman

    (Seattle Children’s Research Institute)

  • Joe Olvera

    (Washington National Primate Research Center)

  • Scott N. Furlan

    (Seattle Children’s Research Institute
    University of Washington)

  • Hengqi Zheng

    (Seattle Children’s Research Institute
    University of Washington)

  • Agne Taraseviciute

    (Seattle Children’s Research Institute
    University of Washington)

  • Daniel J. Hunt

    (Seattle Children’s Research Institute)

  • Kayla Betz

    (Seattle Children’s Research Institute)

  • Jennifer F. Lane

    (Washington National Primate Research Center
    Montana State University)

  • Keith Vogel

    (Washington National Primate Research Center)

  • Charlotte E. Hotchkiss

    (Washington National Primate Research Center)

  • Cassie Moats

    (Washington National Primate Research Center)

  • Audrey Baldessari

    (Washington National Primate Research Center)

  • Robert D. Murnane

    (Washington National Primate Research Center)

  • Christopher English

    (Washington National Primate Research Center)

  • Cliff A. Astley

    (Washington National Primate Research Center)

  • Solomon Wangari

    (Washington National Primate Research Center)

  • Brian Agricola

    (Washington National Primate Research Center)

  • Joel Ahrens

    (Washington National Primate Research Center)

  • Naoto Iwayama

    (Washington National Primate Research Center)

  • Andrew May

    (Washington National Primate Research Center)

  • Laurence Stensland

    (University of Washington)

  • Meei-Li W. Huang

    (University of Washington)

  • Keith R. Jerome

    (University of Washington
    Fred Hutchinson Cancer Research Center)

  • Hans-Peter Kiem

    (Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N
    University of Washington
    University of Washington)

  • Leslie S. Kean

    (Seattle Children’s Research Institute
    University of Washington
    University of Washington
    Boston Children’s Hospital and the Dana-Farber Cancer Institute)

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.

Suggested Citation

  • Lucrezia Colonna & Christopher W. Peterson & John B. Schell & Judith M. Carlson & Victor Tkachev & Melanie Brown & Alison Yu & Sowmya Reddy & Willi M. Obenza & Veronica Nelson & Patricia S. Polacino &, 2018. "Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06736-7
    DOI: 10.1038/s41467-018-06736-7
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    Cited by:

    1. Lianhui Sun & Yuan Zhang & Boyu Yang & Sijun Sun & Pengshan Zhang & Zai Luo & Tingting Feng & Zelin Cui & Ting Zhu & Yuming Li & Zhengjun Qiu & Guangjian Fan & Chen Huang, 2023. "Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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