EBV renders B cells susceptible to HIV-1 in humanized mice

Donal McHugh; Renier Myburgh; Nicole Caduff; Michael Spohn; Yik Lim Kok; Christian W. Keller; Anita Murer; Bithi Chatterjee; Julia Rühl; Christine Engelmann; Obinna Chijioke; Isaak Quast; Mohaned Shilaih; Victoria P. Strouvelle; Kathrin Neumann; Thomas Menter; Stephan Dirnhofer; Janice Kp Lam; Kwai F. Hui; Simon Bredl; Erika Schlaepfer; Silvia Sorce; Andrea Zbinden; Riccarda Capaul; Jan D. Lünemann; Adriano Aguzzi; Alan Ks Chiang; Werner Kempf; Alexandra Trkola; Karin J. Metzner; Markus G. Manz; Adam Grundhoff; Roberto F. Speck; Christian Münz

doi:10.26508/lsa.202000640

EBV renders B cells susceptible to HIV-1 in humanized mice

Donal McHugh, Renier Myburgh, Nicole Caduff, Michael Spohn, Yik Lim Kok, Christian W. Keller, Anita Murer, Bithi Chatterjee, Julia Rühl, Christine Engelmann, Obinna Chijioke, Isaak Quast, Mohaned Shilaih, Victoria P. Strouvelle, Kathrin Neumann, Thomas Menter, Stephan Dirnhofer, Janice Kp Lam, Kwai F. Hui, Simon BredlErika Schlaepfer, Silvia Sorce, Andrea Zbinden, Riccarda Capaul, Jan D. Lünemann, Adriano Aguzzi, Alan Ks Chiang, Werner Kempf, Alexandra Trkola, Karin J. Metzner, Markus G. Manz, Adam Grundhoff, Roberto F. Speck, Christian Münz

Immunology Alfred Hospital

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

28 Citations (Scopus)

Abstract

HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses are linked to AIDS-associated lymphomas. We found that EBV, which transforms B cells, renders them susceptible to HIV-1 infection in a CXCR4 and CD4-dependent manner in vitro and that CXCR4-tropic HIV-1 integrates into the genome of these B cells with the same molecular profile as in autologous CD4+ T cells. In addition, we established a humanized mouse model to investigate the in vivo interactions of EBV and HIV-1 upon coinfection. The respective mice that reconstitute human immune system components upon transplantation with CD34+ human hematopoietic progenitor cells could recapitulate aspects of EBV and HIV immunobiology observed in dual-infected patients. Upon coinfection of humanized mice, EBV/HIV dual-infected B cells could be detected, but were susceptible to CD8+ T-cell-mediated immune control.

Original language	English
Article number	e202000640
Number of pages	19
Journal	Life Science Alliance
Volume	3
Issue number	8
DOIs	https://doi.org/10.26508/lsa.202000640
Publication status	Published - 1 Aug 2020

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McHugh, D., Myburgh, R., Caduff, N., Spohn, M., Kok, Y. L., Keller, C. W., Murer, A., Chatterjee, B., Rühl, J., Engelmann, C., Chijioke, O., Quast, I., Shilaih, M., Strouvelle, V. P., Neumann, K., Menter, T., Dirnhofer, S., Lam, J. K., Hui, K. F., ... Münz, C. (2020). EBV renders B cells susceptible to HIV-1 in humanized mice. Life Science Alliance, 3(8), Article e202000640. https://doi.org/10.26508/lsa.202000640

@article{89a88d0a3e704e9e8aa457a99db4eb4a,

title = "EBV renders B cells susceptible to HIV-1 in humanized mice",

abstract = "HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses are linked to AIDS-associated lymphomas. We found that EBV, which transforms B cells, renders them susceptible to HIV-1 infection in a CXCR4 and CD4-dependent manner in vitro and that CXCR4-tropic HIV-1 integrates into the genome of these B cells with the same molecular profile as in autologous CD4+ T cells. In addition, we established a humanized mouse model to investigate the in vivo interactions of EBV and HIV-1 upon coinfection. The respective mice that reconstitute human immune system components upon transplantation with CD34+ human hematopoietic progenitor cells could recapitulate aspects of EBV and HIV immunobiology observed in dual-infected patients. Upon coinfection of humanized mice, EBV/HIV dual-infected B cells could be detected, but were susceptible to CD8+ T-cell-mediated immune control.",

author = "Donal McHugh and Renier Myburgh and Nicole Caduff and Michael Spohn and Kok, {Yik Lim} and Keller, {Christian W.} and Anita Murer and Bithi Chatterjee and Julia R{\"u}hl and Christine Engelmann and Obinna Chijioke and Isaak Quast and Mohaned Shilaih and Strouvelle, {Victoria P.} and Kathrin Neumann and Thomas Menter and Stephan Dirnhofer and Lam, {Janice Kp} and Hui, {Kwai F.} and Simon Bredl and Erika Schlaepfer and Silvia Sorce and Andrea Zbinden and Riccarda Capaul and L{\"u}nemann, {Jan D.} and Adriano Aguzzi and Chiang, {Alan Ks} and Werner Kempf and Alexandra Trkola and Metzner, {Karin J.} and Manz, {Markus G.} and Adam Grundhoff and Speck, {Roberto F.} and Christian M{\"u}nz",

year = "2020",

month = aug,

day = "1",

doi = "10.26508/lsa.202000640",

language = "English",

volume = "3",

journal = "Life Science Alliance",

issn = "2575-1077",

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McHugh, D, Myburgh, R, Caduff, N, Spohn, M, Kok, YL, Keller, CW, Murer, A, Chatterjee, B, Rühl, J, Engelmann, C, Chijioke, O, Quast, I, Shilaih, M, Strouvelle, VP, Neumann, K, Menter, T, Dirnhofer, S, Lam, JK, Hui, KF, Bredl, S, Schlaepfer, E, Sorce, S, Zbinden, A, Capaul, R, Lünemann, JD, Aguzzi, A, Chiang, AK, Kempf, W, Trkola, A, Metzner, KJ, Manz, MG, Grundhoff, A, Speck, RF & Münz, C 2020, 'EBV renders B cells susceptible to HIV-1 in humanized mice', Life Science Alliance, vol. 3, no. 8, e202000640. https://doi.org/10.26508/lsa.202000640

TY - JOUR

T1 - EBV renders B cells susceptible to HIV-1 in humanized mice

AU - McHugh, Donal

AU - Myburgh, Renier

AU - Caduff, Nicole

AU - Spohn, Michael

AU - Kok, Yik Lim

AU - Keller, Christian W.

AU - Murer, Anita

AU - Chatterjee, Bithi

AU - Rühl, Julia

AU - Engelmann, Christine

AU - Chijioke, Obinna

AU - Quast, Isaak

AU - Shilaih, Mohaned

AU - Strouvelle, Victoria P.

AU - Neumann, Kathrin

AU - Menter, Thomas

AU - Dirnhofer, Stephan

AU - Lam, Janice Kp

AU - Hui, Kwai F.

AU - Bredl, Simon

AU - Schlaepfer, Erika

AU - Sorce, Silvia

AU - Zbinden, Andrea

AU - Capaul, Riccarda

AU - Lünemann, Jan D.

AU - Aguzzi, Adriano

AU - Chiang, Alan Ks

AU - Kempf, Werner

AU - Trkola, Alexandra

AU - Metzner, Karin J.

AU - Manz, Markus G.

AU - Grundhoff, Adam

AU - Speck, Roberto F.

AU - Münz, Christian

PY - 2020/8/1

Y1 - 2020/8/1

N2 - HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses are linked to AIDS-associated lymphomas. We found that EBV, which transforms B cells, renders them susceptible to HIV-1 infection in a CXCR4 and CD4-dependent manner in vitro and that CXCR4-tropic HIV-1 integrates into the genome of these B cells with the same molecular profile as in autologous CD4+ T cells. In addition, we established a humanized mouse model to investigate the in vivo interactions of EBV and HIV-1 upon coinfection. The respective mice that reconstitute human immune system components upon transplantation with CD34+ human hematopoietic progenitor cells could recapitulate aspects of EBV and HIV immunobiology observed in dual-infected patients. Upon coinfection of humanized mice, EBV/HIV dual-infected B cells could be detected, but were susceptible to CD8+ T-cell-mediated immune control.

AB - HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses are linked to AIDS-associated lymphomas. We found that EBV, which transforms B cells, renders them susceptible to HIV-1 infection in a CXCR4 and CD4-dependent manner in vitro and that CXCR4-tropic HIV-1 integrates into the genome of these B cells with the same molecular profile as in autologous CD4+ T cells. In addition, we established a humanized mouse model to investigate the in vivo interactions of EBV and HIV-1 upon coinfection. The respective mice that reconstitute human immune system components upon transplantation with CD34+ human hematopoietic progenitor cells could recapitulate aspects of EBV and HIV immunobiology observed in dual-infected patients. Upon coinfection of humanized mice, EBV/HIV dual-infected B cells could be detected, but were susceptible to CD8+ T-cell-mediated immune control.

UR - http://www.scopus.com/inward/record.url?scp=85087015158&partnerID=8YFLogxK

U2 - 10.26508/lsa.202000640

DO - 10.26508/lsa.202000640

M3 - Article

C2 - 32576602

AN - SCOPUS:85087015158

SN - 2575-1077

VL - 3

JO - Life Science Alliance

JF - Life Science Alliance

IS - 8

M1 - e202000640

ER -

EBV renders B cells susceptible to HIV-1 in humanized mice

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