T-cell and B-cell perturbations identify distinct differences in HIV-2 compared with HIV-1-induced immunodeficiency

Abstract

Background For unknown reasons, HIV-2 is less pathogenic than HIV-1, and HIV-2 induced immunodeficiency may be different from that caused by HIV-1. Previous immunological studies have hinted at possible shifts in both T and B-cell subsets, which we aimed to characterize further. Methods From an HIV clinic in Guinea-Bissau, 63 HIV-2, 83 HIV-1, and 26 HIV negative participants were included. All HIV infected participants were ART naïve. The following cell subsets were analysed by flow cytometry; T cells (maturation and activation), regulatory T cells, and B cells (maturation and activation). Results After standardizing for sex, age, and CD4+ T cell count HIV-2 had 0.938 log10 copies/mL lower HIV RNA levels than the HIV-1 infected patients. Whereas T-cell maturation and regulatory T-cell profiles were similar between patients, HIV-2 infected patients had higher proportions of CD8+CD28+ and lower proportions of CD8+PD-1+ T cells than HIV-1 infected patients. This finding was independent of HIV RNA levels. HIV-2 was also associated with a more preserved proportion of naïve B cells. Conclusion HIV-2 is characterized by lower viral load, and lower T-cell activation, which may account for the slower disease progression.

HIV-2 as a model to identify a functional HIV cure

“…The viral set-point has been suggested to be 10–28 fold lower in HIV-2, with lower levels of viraemia persisting into clinical stages of disease [17, 18]. As a consequence, HIV-2 infection is characterized by lower transmission rates at both the horizontal and vertical levels [19, 20].…”

“…In particular, HIV-2 Gag-specific T-cell responses have been shown to correlate with virus control [59, 61, 62]. Similarly, CD8+ T-cells co-expressing CD28 have been associated with controlled HIV-2 infection [18, 64]. Strikingly, when subjects from the “Caió cohort” with high and undetectable viral loads were compared, the main distinguishing feature was CD8+ T-cell responses to Gag, which were absent in 52% of viraemic participants (the “Caió cohort” was a large community-based cohort from the small rural village Caió, Guinea-Bissau) [63].…”

“…Furthermore, the function of natural killer (NK) cells appears more well-preserved during asymptomatic HIV-2 compared with HIV-1 infection, whereas the functionality of these cells seem to drop to levels found during HIV-1 infection with declining CD4+ T-cells [68]. Similarly to HIV-1 infection, chronic immune activation is linked to immunopathogenesis and progressive disease in HIV-2 infection [18, 69–75]. Elevated frequencies of T-cells expressing markers of activation and exhaustion appear to distinguish HIV-2 infected individuals that progress despite no or low level viraemia, which could be the consequence of long infection duration and/or virus replication not mirrored by plasma RNA levels [18, 70–72].…”

“…Similarly to HIV-1 infection, chronic immune activation is linked to immunopathogenesis and progressive disease in HIV-2 infection [18, 69–75]. Elevated frequencies of T-cells expressing markers of activation and exhaustion appear to distinguish HIV-2 infected individuals that progress despite no or low level viraemia, which could be the consequence of long infection duration and/or virus replication not mirrored by plasma RNA levels [18, 70–72]. Although these findings could suggest that aviraemic HIV-2 infected individuals should be offered ART, there remains a group of aviraemic individuals with HIV-2 infection without evidence of immune activation who may not necessarily benefit from therapy [70].…”

Computational Modulation of the V3 Region of Glycoprotein gp125 of HIV-2

“…Distinct from HIV-1, HIV-2 is less virulent and only a small percentage of HIV-2 infected patients progress to AIDS. Disease progression is much lower relative to HIV-1 infected patients, leading to a high percentage of asymptomatic patients, lower transmission rate, and longer latency, resulting in a longer disease-free survival [5]. The mechanisms that enable the human host to better control the HIV-2 infection by itself are far from being completely understood.…”