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HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication

HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication
HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication

The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-β 3-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.

1933-0219
236-248
Fernandes, S.M.
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Pires, A.R.
ce99015d-c054-4678-9e9a-724517784ac3
Matoso, P.
d1fef3e9-5b91-416a-bbae-160945b60e42
Ferreira, C.
c9dd70d2-1d8f-4677-adbd-82955bc046bf
Nunes-Cabaço, H.
fd3eb459-a1b1-4a0b-abc6-d3d460ba09b3
Correia, L.
cb7daf2b-5f23-4b36-a73e-878f3c212b05
Valadas, E.
b0196a2d-140b-4f24-bc7e-278fe88c0327
Poças, J.
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Pacheco, A.P.
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Veiga-Fernandes, H.
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Foxall, R.B.
cfe3a818-a281-4bcb-8889-e1d0b591117c
Sousa, A.E.
52138768-346f-4ec8-ae1f-8b1f71e386ff
Fernandes, S.M.
1c4a0876-6442-46bf-a76a-f044fc895f77
Pires, A.R.
ce99015d-c054-4678-9e9a-724517784ac3
Matoso, P.
d1fef3e9-5b91-416a-bbae-160945b60e42
Ferreira, C.
c9dd70d2-1d8f-4677-adbd-82955bc046bf
Nunes-Cabaço, H.
fd3eb459-a1b1-4a0b-abc6-d3d460ba09b3
Correia, L.
cb7daf2b-5f23-4b36-a73e-878f3c212b05
Valadas, E.
b0196a2d-140b-4f24-bc7e-278fe88c0327
Poças, J.
3a2c0f21-b62e-4834-9d77-b1aa4c67c9ac
Pacheco, A.P.
58f03fb4-176d-40f7-bca7-458e60729e64
Veiga-Fernandes, H.
7d6d31fd-7662-4cf7-bb13-c2fc1f12b946
Foxall, R.B.
cfe3a818-a281-4bcb-8889-e1d0b591117c
Sousa, A.E.
52138768-346f-4ec8-ae1f-8b1f71e386ff

Fernandes, S.M., Pires, A.R., Matoso, P., Ferreira, C., Nunes-Cabaço, H., Correia, L., Valadas, E., Poças, J., Pacheco, A.P., Veiga-Fernandes, H., Foxall, R.B. and Sousa, A.E. (2017) HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication. Mucosal Immunology, 11 (1), 236-248. (doi:10.1038/mi.2017.44).

Record type: Article

Abstract

The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-β 3-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3+ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. Moreover, IL-22-producing innate lymphoid cells and IL-22-induced antimicrobial peptides and mucins were maintained. In agreement, the epithelium histology was preserved, including tight junction protein zonula occludens (ZO-1) levels. Furthermore, in vitro infection of colon epithelia with primary isolates revealed no HIV-2 impact on ZO-1 expression. Notably, sigmoid transcriptional levels of CCL20 and CCL28 were significantly increased, in direct correlation with GM-CSF, indicating a local response able to enhance CD4 T-cell recruitment. In conclusion, maintenance of mucosal integrity in HIV-2 infection was associated with T-cell recruitment responses, potentially counteracting CD4 T-cell depletion due to HIV-2 replication. These data have unique implications for the design of therapies targeting gut homeostasis in HIV-1 infection and other chronic inflammatory settings.

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More information

Accepted/In Press date: 10 April 2017
e-pub ahead of print date: 17 May 2017
Published date: 17 May 2017

Identifiers

Local EPrints ID: 418958
URI: http://eprints.soton.ac.uk/id/eprint/418958
ISSN: 1933-0219
PURE UUID: 5ed92662-172d-483f-947c-cdde4e4c547c

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Date deposited: 27 Mar 2018 16:30
Last modified: 17 Mar 2024 12:01

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Contributors

Author: S.M. Fernandes
Author: A.R. Pires
Author: P. Matoso
Author: C. Ferreira
Author: H. Nunes-Cabaço
Author: L. Correia
Author: E. Valadas
Author: J. Poças
Author: A.P. Pacheco
Author: H. Veiga-Fernandes
Author: R.B. Foxall
Author: A.E. Sousa

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