Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques

Helen L. Wu; Kathleen Busman-Sahay; Whitney C. Weber; Courtney M. Waytashek; Carla D. Boyle; Katherine B. Bateman; Jason S. Reed; Joseph M. Hwang; Christine Shriver-Munsch; Tonya Swanson; Mina Northrup; Kimberly Armantrout; Heidi Price; Mitch Robertson-LeVay; Samantha Uttke; Mithra R. Kumar; Emily J. Fray; Sol Taylor-Brill; Stephen Bondoc; Rebecca Agnor; Stephanie L. Junell; Alfred W. Legasse; Cassandra Moats; Rachele M. Bochart; Joseph Sciurba; Benjamin N. Bimber; Michelle N. Sullivan; Brandy Dozier; Rhonda P. MacAllister; Theodore R. Hobbs; Lauren D. Martin; Angela Panoskaltsis-Mortari; Lois M.A. Colgin; Robert F. Siliciano; Janet D. Siliciano; Jacob D. Estes; Jeremy V. Smedley; Michael K. Axthelm; Gabrielle Meyers; Richard T. Maziarz; Benjamin J. Burwitz; Jeffrey J. Stanton; Jonah B. Sacha

doi:10.1016/j.immuni.2023.04.019

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques

Helen L. Wu, Kathleen Busman-Sahay, Whitney C. Weber, Courtney M. Waytashek, Carla D. Boyle, Katherine B. Bateman, Jason S. Reed, Joseph M. Hwang, Christine Shriver-Munsch, Tonya Swanson, Mina Northrup, Kimberly Armantrout, Heidi Price, Mitch Robertson-LeVay, Samantha Uttke, Mithra R. Kumar, Emily J. Fray, Sol Taylor-Brill, Stephen Bondoc, Rebecca AgnorStephanie L. Junell, Alfred W. Legasse, Cassandra Moats, Rachele M. Bochart, Joseph Sciurba, Benjamin N. Bimber, Michelle N. Sullivan, Brandy Dozier, Rhonda P. MacAllister, Theodore R. Hobbs, Lauren D. Martin, Angela Panoskaltsis-Mortari, Lois M.A. Colgin, Robert F. Siliciano, Janet D. Siliciano, Jacob D. Estes, Jeremy V. Smedley, Michael K. Axthelm, Gabrielle Meyers, Richard T. Maziarz, Benjamin J. Burwitz, Jeffrey J. Stanton, Jonah B. Sacha

Research output: Contribution to journal › Article › peer-review

Abstract

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5^Δ32/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.

Original language	English (US)
Pages (from-to)	1649-1663.e5
Journal	Immunity
Volume	56
Issue number	7
DOIs	https://doi.org/10.1016/j.immuni.2023.04.019
State	Published - Jul 11 2023

Keywords

CCR5
GVHD
HIV
HSCT
SIV

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2023.04.019

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Wu, H. L., Busman-Sahay, K., Weber, W. C., Waytashek, C. M., Boyle, C. D., Bateman, K. B., Reed, J. S., Hwang, J. M., Shriver-Munsch, C., Swanson, T., Northrup, M., Armantrout, K., Price, H., Robertson-LeVay, M., Uttke, S., Kumar, M. R., Fray, E. J., Taylor-Brill, S., Bondoc, S., ... Sacha, J. B. (2023). Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques. Immunity, 56(7), 1649-1663.e5. https://doi.org/10.1016/j.immuni.2023.04.019

Wu, HL, Busman-Sahay, K, Weber, WC, Waytashek, CM, Boyle, CD, Bateman, KB, Reed, JS, Hwang, JM, Shriver-Munsch, C, Swanson, T, Northrup, M, Armantrout, K, Price, H, Robertson-LeVay, M, Uttke, S, Kumar, MR, Fray, EJ, Taylor-Brill, S, Bondoc, S, Agnor, R, Junell, SL, Legasse, AW, Moats, C, Bochart, RM, Sciurba, J, Bimber, BN, Sullivan, MN, Dozier, B, MacAllister, RP, Hobbs, TR, Martin, LD, Panoskaltsis-Mortari, A, Colgin, LMA, Siliciano, RF , Siliciano, JD, Estes, JD, Smedley, JV, Axthelm, MK, Meyers, G, Maziarz, RT, Burwitz, BJ, Stanton, JJ & Sacha, JB 2023, 'Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques', Immunity, vol. 56, no. 7, pp. 1649-1663.e5. https://doi.org/10.1016/j.immuni.2023.04.019

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title = "Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques",

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.",

keywords = "CCR5, GVHD, HIV, HSCT, SIV",

author = "Wu, {Helen L.} and Kathleen Busman-Sahay and Weber, {Whitney C.} and Waytashek, {Courtney M.} and Boyle, {Carla D.} and Bateman, {Katherine B.} and Reed, {Jason S.} and Hwang, {Joseph M.} and Christine Shriver-Munsch and Tonya Swanson and Mina Northrup and Kimberly Armantrout and Heidi Price and Mitch Robertson-LeVay and Samantha Uttke and Kumar, {Mithra R.} and Fray, {Emily J.} and Sol Taylor-Brill and Stephen Bondoc and Rebecca Agnor and Junell, {Stephanie L.} and Legasse, {Alfred W.} and Cassandra Moats and Bochart, {Rachele M.} and Joseph Sciurba and Bimber, {Benjamin N.} and Sullivan, {Michelle N.} and Brandy Dozier and MacAllister, {Rhonda P.} and Hobbs, {Theodore R.} and Martin, {Lauren D.} and Angela Panoskaltsis-Mortari and Colgin, {Lois M.A.} and Siliciano, {Robert F.} and Siliciano, {Janet D.} and Estes, {Jacob D.} and Smedley, {Jeremy V.} and Axthelm, {Michael K.} and Gabrielle Meyers and Maziarz, {Richard T.} and Burwitz, {Benjamin J.} and Stanton, {Jeffrey J.} and Sacha, {Jonah B.}",

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month = jul,

day = "11",

doi = "10.1016/j.immuni.2023.04.019",

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T1 - Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques

AU - Wu, Helen L.

AU - Busman-Sahay, Kathleen

AU - Weber, Whitney C.

AU - Waytashek, Courtney M.

AU - Boyle, Carla D.

AU - Bateman, Katherine B.

AU - Reed, Jason S.

AU - Hwang, Joseph M.

AU - Shriver-Munsch, Christine

AU - Swanson, Tonya

AU - Northrup, Mina

AU - Armantrout, Kimberly

AU - Price, Heidi

AU - Robertson-LeVay, Mitch

AU - Uttke, Samantha

AU - Kumar, Mithra R.

AU - Fray, Emily J.

AU - Taylor-Brill, Sol

AU - Bondoc, Stephen

AU - Agnor, Rebecca

AU - Junell, Stephanie L.

AU - Legasse, Alfred W.

AU - Moats, Cassandra

AU - Bochart, Rachele M.

AU - Sciurba, Joseph

AU - Bimber, Benjamin N.

AU - Sullivan, Michelle N.

AU - Dozier, Brandy

AU - MacAllister, Rhonda P.

AU - Hobbs, Theodore R.

AU - Martin, Lauren D.

AU - Panoskaltsis-Mortari, Angela

AU - Colgin, Lois M.A.

AU - Siliciano, Robert F.

AU - Siliciano, Janet D.

AU - Estes, Jacob D.

AU - Smedley, Jeremy V.

AU - Axthelm, Michael K.

AU - Meyers, Gabrielle

AU - Maziarz, Richard T.

AU - Burwitz, Benjamin J.

AU - Stanton, Jeffrey J.

AU - Sacha, Jonah B.

PY - 2023/7/11

Y1 - 2023/7/11

N2 - 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.

AB - 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.

KW - CCR5

KW - GVHD

KW - HIV

KW - HSCT

KW - SIV

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AN - SCOPUS:85163166868

SN - 1074-7613

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SP - 1649-1663.e5

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ER -

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques

Abstract

Keywords

ASJC Scopus subject areas

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