HTLV-1/-2 and HIV-1 co-infections: retroviral interference on host immune status

Abstract

The human retroviruses HIV-1 and HTLV-1/HTLV-2 share similar routes of transmission but cause significantly different diseases. In this review we have outlined the immune mediated mechanisms by which HTLVs affect HIV-1 disease in co-infected hosts. During co-infection with HIV-1, HTLV-2 modulates the cellular microenvironment favoring its own viability and inhibiting HIV-1 progression. This is achieved when the HTLV-2 proviral load is higher than that of HIV-1, and thanks to the ability of HTLV-2 to: (i) up-regulate viral suppressive CCL3L1 chemokine expression; (ii) overcome HIV-1 capacity to activate the JAK/STAT pathway; (iii) reduce the activation of T and NK cells; (iv) modulate the host miRNA profiles. These alterations of immune functions have been mainly attributed to the effects of the HTLV-2 regulatory protein Tax and suggest that HTLV-2 exerts a protective role against HIV-1 infection. Contrary to HIV-1/HTLV-2, the effect of HIV-1/HTLV-1 co-infection on immunological and pathological conditions is still controversial. There is evidence that indicates a worsening of HIV-1 infection, while other evidence does not show clinically relevant effects in HIV-positive people. Possible differences on innate immune mechanisms and a particularly impact on NK cells are becoming evident. The differences between the two HIV-1/HTLV-1 and HIV-1/HTLV-2 co-infections are highlighted and further discussed.

HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment

“…The effect of HIV-1/HTLV-1 co-infection on the pathological conditions seems clearer and converges with a worsening of symptoms linked to HIV-1 or HTLV-1 infection [ 134 , 153 ]. Although the number of documented HIV-1/HTLV-1 co-infected cohorts remains low, it is believed that HTLV-1 worsens HIV-1 infection by accelerating progression to AIDS or increasing mortality [ 154 ].…”

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

“…On the other hand, it seems that HTLV-2 may confer certain immunological protection against HIV-1, delaying the natural history of the disease [125]. The proposed mechanism would be an interaction of the Tax-2 protein at several levels of the replicative cycle of HIV-1 and the alteration of several immunological processes [126].…”

NF-κB and MicroRNA Deregulation Mediated by HTLV-1 Tax and HBZ

“…Comparative studies of HTLV-1 and HTLV-2 have been aimed at identifying peculiar properties of HTLV-1 that may explain its oncogenicity. Cohort studies of HIV-infected persons have indicated that HTLV-2 might be protective against HIV-1 replication, although the role of HTLV-1 and 2 in HIV co-infection remains controversial [18].…”