title: 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.
authors: Infectious Diseases Division, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Z
authors: Z
authors: Oo
authors: C S
authors: CS
authors: Barrios
authors: L
authors: L
authors: Castillo
authors: M A
authors: MA
authors: Beilke
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D019742:Chemokines, CC / Q000096:biosynthesis*; D060085:Coinfection / Q000276:immunology* / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D015490:HTLV-I Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015491:HTLV-II Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification; D015367:Human T-lymphotropic virus 2 / Q000302:isolation & purification; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000096:biosynthesis*
chemical_list: C584933:CCR5 protein, human; D019742:Chemokines, CC; D019713:Receptors, CCR5
keywords: Tax1; Tax2; innate immunity; viral coinfection