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

Emil Johansson; Priscilla F Kerkman; Lydia Scharf; Jacob Lindman; Zsófia I Szojka; Fredrik Månsson; Antonio Biague; Patrik Medstrand; Hans Norrgren; Marcus Buggert; Annika C Karlsson; Mattias N E Forsell; Joakim Esbjörnsson; Marianne Jansson; The Swegub Core Group

doi:10.3390/cells11193142

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

Cells. 2022 Oct 6;11(19):3142. doi: 10.3390/cells11193142.

Authors

Emil Johansson¹, Priscilla F Kerkman^{2

3}, Lydia Scharf⁴, Jacob Lindman⁵, Zsófia I Szojka¹, Fredrik Månsson⁶, Antonio Biague⁷, Patrik Medstrand⁶, Hans Norrgren⁵, Marcus Buggert⁸, Annika C Karlsson⁴, Mattias N E Forsell², Joakim Esbjörnsson^{6

9}, Marianne Jansson¹, The Swegub Core Group

Affiliations

¹ Department of Laboratory Medicine, Lund University, 22184 Lund, Sweden.
² Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden.
³ Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
⁴ Department of Laboratory Medicine, Karolinska Institutet, 14152 Huddinge, Sweden.
⁵ Department of Clinical Sciences Lund, Lund University, 22184 Lund, Sweden.
⁶ Department of Translational Medicine, Lund University, 20502 Malmö, Sweden.
⁷ National Laboratory for Public Health, Bissau 1041, Guinea-Bissau.
⁸ Department of Medicine Huddinge, Karolinska Institutet, 14186 Stockholm, Sweden.
⁹ Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.

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-bet^highCD95^highCD27^int and proliferating T-bet⁺CD95^highCD27⁺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.

Keywords: B-cell phenotype; CD95; HIV-1; HIV-2; T-bet; immune perturbations; viremia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cluster Analysis
HIV Infections*
HIV Seropositivity*
HIV-1* / physiology
HIV-2
Humans
Viremia

Grants and funding

This work was supported by grants given by The Swedish Research Council to M.J. (2016-02285, 2019-01439), J.E. (2020-06262) and M.N.E.F. (2020-06235), and by The Swedish Fund for Research without Animal Experiments to MJ (N2019-0009, F2021-0010).