title: 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.
authors.affiliation: GEMIB Laboratory, Center for Medical Research and Molecular Diagnostics Parma, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pilotti
authors.affiliation: GEMIB Laboratory, Center for Medical Research and Molecular Diagnostics Parma, Italy.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Bianchi
authors.affiliation: Department of Health Sciences, University of Genova Genova, Italy ; Center of Excellence for Biomedical Research, University of Genova Genova, Italy ; IRCCS AOU San Martino-IST Genova Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
authors.affiliation: Department of Health Sciences, University of Genova Genova, Italy ; Center of Excellence for Biomedical Research, University of Genova Genova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bozzano
authors.affiliation: Department of Life and Reproduction Sciences, University of Verona Verona, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Romanelli
authors.affiliation: Department of Life and Reproduction Sciences, University of Verona Verona, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Bertazzoni
authors.affiliation: GEMIB Laboratory, Center for Medical Research and Molecular Diagnostics Parma, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Casoli
keywords: HIV-1; HTLV; JAK/STAT; chemokines; co-infection; cytokines; miRNA; natural killer cells