HTLV-2 Enhances CD8+ T Cell-Mediated HIV-1 Inhibition and Reduces HIV-1 Integrated Proviral Load in People Living with HIV-1

Abstract

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.

Concluding Remarks for Special Issue HTLV-HIV Co-Infections

“…Also, HIV-1 proviral load is associated with HTLV-2 infection. The authors confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals [1].…”

Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review

“…In contrast, coinfection of HIV with HTLV-2, another type of HTLV that is non-pathogenic but rarely associated with HAM/TSP, showed slow T cell depletion and AIDS progression, with higher HIV-1 viral control and lower mortality rates [79]. This effect is mediated via CTL expansion induced by HTLV-2, including a high rate of the effector memory phenotype and increased levels of granzymes A and B and perforin [79]. Although a case of ATL in an HIV-1-positive patient has been reported A B [80], more evidence is needed to determine the possibility of patients with HIV having an increased risk of ATL.…”

“…HTLV-1 activates CD4+ T cells, and Tax upregulates HIV-1 infection [78]. In contrast, coinfection of HIV with HTLV-2, another type of HTLV that is non-pathogenic but rarely associated with HAM/TSP, showed slow T cell depletion and AIDS progression, with higher HIV-1 viral control and lower mortality rates [79]. This effect is mediated via CTL expansion induced by HTLV-2, including a high rate of the effector memory phenotype and increased levels of granzymes A and B and perforin [79].…”

Understanding the Immunopathology of HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: A Comprehensive Review

“…HTLV-1 activates CD4+ T cells, and Tax upregulates HIV-1 infection [78]. In contrast, HIV coinfection with HTLV-2, another type of HTLV that is non-pathogenic but rarely associated with HAM/TSP, is associated with slow T-cell depletion and AIDS progression, with higher HIV-1 viral control and lower mortality rates [79]. This effect is mediated by CTL expansion induced by HTLV-2, including a high rate of the effector memory phenotype and increased levels of granzymes A and B and perforin [79].…”

“…In contrast, HIV coinfection with HTLV-2, another type of HTLV that is non-pathogenic but rarely associated with HAM/TSP, is associated with slow T-cell depletion and AIDS progression, with higher HIV-1 viral control and lower mortality rates [79]. This effect is mediated by CTL expansion induced by HTLV-2, including a high rate of the effector memory phenotype and increased levels of granzymes A and B and perforin [79]. Although a case of ATL has been reported in an HIV-1-positive patient [80], more evidence is needed to determine whether individuals with HIV infection have an increased risk of ATL.…”