Emil Johansson[1], Priscilla F. Kerkman[2], Lydia Scharf[3], Jacob Lindman[4], Fredrik Månsson[5], Antonio Biague[6], Patrik Medstrand[5], Hans Norrgren[4], Marcus Buggert[7], Annika C. Karlsson[3], Joakim Esbjörnsson[5,8*], Mattias Forsell[2*], Marianne Jansson[1*] and the SWEGUB CORE Group

Affiliates

Department of Laboratory Medicine, Lund University, Lund, Sweden[1] Department of Clinical Microbiology, Umeå University, Sweden[2] Department of Laboratory Medicine, Karolinska Institutet, Sweden[3] Department of Clinical Sciences Lund, Lund University, Sweden[4] Department of Translational Medicine, Lund University, Sweden[5] National Laboratory for Public Health, Guinea-Bissau[6] Department of Medicine Huddinge, Karolinska Institutet, Sweden[7] Nuffield Department of Medicine, University of Oxford, United Kingdom[8] These authors contributed equally to this study[*]

Abstract

The time to AIDS onset after an HIV-2 infection is approximately twice as long compared to after an HIV-1 infection. Still, despite potent adaptive immune responses and reduced viremia, HIV-2 infected individuals display signs of chronic immune activation. In HIV-1 infected individuals, B-cell activation and exhaustion has been suggested to be driven by continuous exposure to HIV-1 antigens. However, the contribution of viremia to B-cell perturbations in HIV-2 infected individuals is still largely unexplored. In this study, we used polychromatic flow cytometry, unsupervised consensus hierarchical clustering algorithms and pseudotime trajectory inference to characterize B-cell phenotypes in HIV-1 or HIV-2 infected and in HIV seronegative individuals from a cohort in Guinea-Bissau. We observed increased frequencies of clusters containing hyperactivated T-bethighCD95+CD27int and proliferating CD95+T-bet+CD27+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, when compared to seronegative individuals. In contrast, these expansions were not observed in HIV-1 infected individuals receiving successful antiretroviral therapy treatment. Finally, pseudotime trajectory inference showed that the 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 also aviremic HIV-2 infected individuals would benefit from antiretroviral treatment.