Background:
Time to AIDS in HIV-2 infection is approximately twice as long compared to in HIV-1 infection. Still, and despite reduced viraemia, HIV-2 infected individuals display signs of chronic immune activation. In HIV-1 infected individuals, the expansion of hyperactivated B-cells, characterized by the expression of the transcription factor T-bet, is driven by continuous antigen exposure. However, the contribution of viraemia to B-cell perturbations in HIV-2 infected individuals remains largely unexplored. Here we set out to determine if B-cell hyperactivation is viraemia dependent during HIV-2 infection, as it has been described for HIV-1 infection.
Methods:
We used polychromatic flow cytometry to immunophenotype B-cells from HIV-1 infected (viraemic (n=8) and successfully ART treated (n=7) individuals), HIV-2 infected (viraemic (n=8) and treatment naïve aviraemic (n=12) individuals), and HIV seronegative (n=25) individuals from Guinea-Bissau. We performed consensus hierarchical cluster analysis on the flow cytometry data, using the FlowSOM R packages, to define the impact of HIV-1 or HIV-2 infections on the expansion or depletion of B-cell populations. Plasma proteins were quantified using an Olink Proteomics panel. Frequencies of identified B-cell populations were correlated with concentrations of Th1 associated proinflammatory cytokines.
Results:
We observed increased frequencies of clusters containing hyperactivated T-bethighCD95+CD27int and proliferating CD95+T-bet+CD27+CD71+ memory B-cells in viraemic HIV-1 (p< 0.001 and p< 0.001, respectively), viraemic HIV-2 (p< 0.001 and p=0.014, respectively), and in treatment naïve aviraemic 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, the frequency of the hyperactivated Tbethigh memory B-cells showed a moderate to strong correlation with plasma concentrations of proinflammatory Th1-associated cytokines, most prominently TNF-α (r=0.686; p=0.001), IFN-γ (r=0.530; p=0.020), CXCL9 (r=0.619; p=0.005) and CXCL10 (r=674; p=0.002) in HIV-2 infected individuals.
Conclusions:
In contrast to successfully ART treated HIV-1 infected individuals; treatment naïve aviraemic HIV-2 infected individuals showed B-cell perturbations. Our data therefore suggest that aviraemic HIV-2 infected individuals are likely to benefit from antiretroviral treatment.