HTLV-1 Tax activates HIV-1 transcription in latency models

• Autor(a) principal: Victor Emmanuel Viana Geddes
• Data de Publicação: 2017
• Outros Autores: Diego Pandeló José, Fabio E. Leal, Douglas F. Nixon, Amilcar Tanuri, Renato Santana de Aguiar
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://doi.org/10.1016/j.virol.2017.01.014; http://hdl.handle.net/1843/56337; https://orcid.org/0000-0002-0723-3873; https://orcid.org/0000-0002-3243-5688; https://orcid.org/0000-0002-2801-1786; https://orcid.org/0000-0003-0570-750X
• topic: HIV-1; Latency; HTLV-1; Tax; Tax; Resting cells; HIV (Virus); HTLV-I (Virus)

HIV-1 latency is a major obstacle to HIV-1 eradication. Coinfection with HTLV-1 has been associated with faster progression to AIDS. HTLV-1 encodes the transactivator Tax which can activate both HTLV-1 and HIV-1 transcription. Here, we demonstrate that Tax activates HIV transcription in latent CD4+ T cells. Tax promotes the activation of P-TEFb, releasing CDK9 and Cyclin T1 from inactive forms, promoting transcription elongation and reactivation of latent HIV-1. Tax mutants lacking interaction with the HIV-1-LTR promoter were not able to activate P-TEFb, with no subsequent activation of latent HIV. In HIV-infected primary resting CD4+ T cells, Tax-1 reactivated HIV-1 transcription up to five fold, confirming these findings in an ex vivo latency model. Finally, our results confirms that HTLV-1/Tax hijacks cellular partners, promoting HIV-1 transcription, and this interaction should be further investigated in HIV-1 latency studies in patients with HIV/ HTLV-1 co-infection.