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Hierarchical Clustering and Trajectory Analyses Reveal Viremia-Independent B-Cell Perturbations in HIV-2 Infection

Johansson, Emil LU orcid ; Kerkman, Priscilla F. ; Scharf, Lydia ; Lindman, Jacob LU ; Szojka, Zsófia I. LU ; Månsson, Fredrik LU ; Biague, Antonio ; Medstrand, Patrik LU orcid ; Norrgren, Hans LU and Buggert, Marcus , et al. (2022) In Cells 11(19).
Abstract

Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and... (More)

Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95highCD27int and proliferating T-bet+CD95highCD27+CD71+ memory B-cells in viremic HIV-1 (p < 0.001 and p < 0.001, respectively), viremic HIV-2 (p < 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
B-cell phenotype, CD95, HIV-1, HIV-2, immune perturbations, T-bet, viremia
in
Cells
volume
11
issue
19
article number
3142
publisher
MDPI AG
external identifiers
  • scopus:85139931412
  • pmid:36231103
ISSN
2073-4409
DOI
10.3390/cells11193142
language
English
LU publication?
yes
id
91a6600e-b17f-47eb-a090-cdd005770c9c
date added to LUP
2022-12-14 15:32:25
date last changed
2024-06-23 17:10:52
@article{91a6600e-b17f-47eb-a090-cdd005770c9c,
  abstract     = {{<p>Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Despite reduced viremia, HIV-2-infected individuals display signs of chronic immune activation. In HIV-1-infected individuals, B-cell hyperactivation is driven by continuous antigen exposure. However, the contribution of viremia to B-cell perturbations in HIV-2-infected individuals remains largely unexplored. Here, we used polychromatic flow cytometry, consensus hierarchical clustering and pseudotime trajectory inference to characterize B-cells in HIV-1- or HIV-2-infected and in HIV seronegative individuals. We observed increased frequencies of clusters containing hyperactivated T-bet<sup>high</sup>CD95<sup>high</sup>CD27<sup>int</sup> and proliferating T-bet<sup>+</sup>CD95<sup>high</sup>CD27<sup>+</sup>CD71<sup>+</sup> memory B-cells in viremic HIV-1 (p &lt; 0.001 and p &lt; 0.001, respectively), viremic HIV-2 (p &lt; 0.001 and p = 0.014, respectively) and in treatment-naïve aviremic HIV-2 (p = 0.004 and p = 0.020, respectively)-infected individuals, compared to seronegative individuals. In contrast, these expansions were not observed in successfully treated HIV-1-infected individuals. Finally, pseudotime trajectory inference showed that T-bet-expressing hyperactivated and proliferating memory B-cell populations were located at the terminal end of two trajectories, in both HIV-1 and HIV-2 infections. As the treatment-naïve aviremic HIV-2-infected individuals, but not the successfully ART-treated HIV-1-infected individuals, showed B-cell perturbations, our data suggest that aviremic HIV-2-infected individuals would also benefit from antiretroviral treatment.</p>}},
  author       = {{Johansson, Emil and Kerkman, Priscilla F. and Scharf, Lydia and Lindman, Jacob and Szojka, Zsófia I. and Månsson, Fredrik and Biague, Antonio and Medstrand, Patrik and Norrgren, Hans and Buggert, Marcus and Karlsson, Annika C. and Forsell, Mattias N.E. and Esbjörnsson, Joakim and Jansson, Marianne}},
  issn         = {{2073-4409}},
  keywords     = {{B-cell phenotype; CD95; HIV-1; HIV-2; immune perturbations; T-bet; viremia}},
  language     = {{eng}},
  number       = {{19}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Hierarchical Clustering and Trajectory Analyses Reveal Viremia-Independent B-Cell Perturbations in HIV-2 Infection}},
  url          = {{http://dx.doi.org/10.3390/cells11193142}},
  doi          = {{10.3390/cells11193142}},
  volume       = {{11}},
  year         = {{2022}},
}