Inhibition of HIV-1 replication by HTLV-1/2 Tax proteins in vitro

Medical College of Wisconsin, Medicine, Infectious Diseases, 9200 W. Wisconsin Avenue, Clinical Cancer Center, 5th Floor, Milwaukee, Wisconsin, United States, 53226, 414-805-0746, 414-805-0748
AIDS research and human retroviruses (Impact Factor: 2.33). 03/2013; 29. DOI: 10.1089/AID.2013.0027
Source: PubMed

ABSTRACT Patients with HIV-1 and HTLV-2 coinfections often exhibit a clinical course similar to that seen in HIV-1 infected individuals who are long-term nonprogressors. These findings have been attributed in part to the ability of HTLV-2 to activate production of antiviral chemokines and to downregulate the CCR5 coreceptor on lymphocytes. To further investigate these observations, we tested the ability of recombinant Tax1 and Tax2 proteins to suppress HIV-1 viral replication in vitro. R5-tropic HIV-1 (NLAD8)-infected-PBMCs were treated daily with recombinant Tax1 and Tax2 proteins (dosage range 1-100 pM). Culture supernatants were collected at intervals from days 1 to 22 post-infection and assayed for levels of HIV-1 p24 antigen by ELISA. Treatment of PBMCs with Tax2 protein resulted in significant reduction in HIV-1 p24 antigen levels (p<0.05) at days 10, 14, and 18 post-infection compared to HIV-1-infected or mock-treated PBMCs. This was preceded by the detection of increased levels of CC-chemokines MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5, on days 1-7 of infection. Similar, but less robust inhibition was observed in Tax1 treated PBMCs. These results support the contention that Tax1 and Tax2 play a role in generating antiviral responses against HIV-1 in vivo and in vitro.

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