High levels of CC-chemokine expression and downregulated levels of CCR5 during HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections

Abstract

The human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 are common copathogens among Human Immunodeficiency Virus (HIV)-infected individuals. HTLV-2 may confer a survival benefit among patients with HIV-1/HTLV-2 coinfections, along with lower plasma HIV-1 levels and delayed rates of CD4(+) T-cell decline. These effects have been attributed to the ability of the HTLV-2 viral transactivating Tax2 protein to induce the production of high levels of antiviral CC-chemokines and to downregulate expression of the CCR5 receptor, resulting in impaired entry of HIV-1 into CD4(+) T-cells. This study investigated the innate immunity of coinfected HIV/HTLV individuals by testing the ability of patient PBMCs to produce CC-chemokines in association CCR5 receptor modulation. The cellular proliferative responses of HIV/HTLV coinfected versus HIV monoinfected individuals were also evaluated. Higher levels of MIP-1α, MIP-1β, and RANTES (P < 0.05) were found in HIV-1/HTLV-2 coinfected group compared to HIV-1 monoinfected population. Upregulated levels of RANTES were shown in HIV-1/HTLV-1 after 1 and 3 days of culture (P < 0.05). Lymphocytes from HIV-1/HTLV-2 coinfected individuals showed significant CCR5 downregulation after 1 and 3 days of culture compared to lymphocytes from HIV-1 and uninfected groups (P < 0.05). Lower percentages of CCR5-positive cells were found in HIV-1/HTLV-1 coinfected after 3 days of incubation (P < 0.05). Levels of proliferation were significantly higher in the HIV-1/HTLV-1 group compared to HIV-1 alone (P < 0.05). HTLV-2 and HTLV-1 infections may induce the involvement of innate immunity against HIV-1 via stimulation of CC-chemokines and receptors, potentially modifying CCR5/HIV-1 binding and HIV-1 progression in coinfected individuals.

Prevalence of CCR5delta32 in Northeastern Iran

“…The trans-activating function of Tax protein 2 is attributed to an increased secretion of CCL3L1 [49]. During human T-cell lymphotropic virus type 1 (HTLV)-1 and HTLV-2 infections with CCLs and CCRs, Tax1 and Tax2 may increase innate immunity in the extracellular environment, which may play a major role in regulating innate immunity during co-infection with HIV/ HTLV and inhibiting CCR5/HIV-1 [51]. The CCL3L1 down-regulates CCR5 for the entry of HIV-1, resulting in a long-term non-development status in co-infected patients with the high infection of HTLV-1 and 2 [52].…”

Neurological Aspects of HIV-1/HTLV-1 and HIV-1/HTLV-2 Coinfection

“…• HTLV-1 virions and proteins upregulate HIV-1 infection by activating CD4+ T cells [29][30][31][32] Several pieces of evidence suggest that HTLV suppress the replication of HIV-1 by releasing CC chemokines [30,[37][38][39]. This mechanism may stimulate the innate immunity against HIV-1 through the modification of CCR5/HIV-1 binding and, consequently, hindering the progression of HIV-1-related disease in coinfected individuals [40]. Some soluble factors released by HTLV-1 may increase or suppress HIV-1 infection.…”

STLV-1 as a model for studying HTLV-1 infection

“…Cases of natural coinfection have been reported both in humans and in NHPs: HTLV-1/HIV-1, HTLV-1/HFV, STLV-1/SFV or STLV-1/SIV-1 [67, 107–115]. HIV-1/HTLV-1 coinfection leads to significant increase of HTLV-1 PVL as well as on a possible delay in HIV-1 pathogenesis in humans [107, 108, 116]. Anti-HIV-1 therapy promotes an increase in HTLV-1 PVL in HIV-1/HTLV-1 coinfected carriers.…”