HTLV-1 Tax activates HIV-1 transcription in latency models.
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.
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
Victor Emmanuel Viana
VEV
Geddes
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil; Universidade Federal do Triângulo Mineiro, campus Iturama, Minas Gerais, 38280-000, Brazil.
Diego Pandeló
DP
José
Instituto Nacional de Cancer, Programa de Oncovirologia, Rio de Janeiro, Brazil.
Fabio E
FE
Leal
Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington, DC, USA.
Douglas F
DF
Nixon
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
Amilcar
A
Tanuri
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil. Electronic address: santana@biologia.ufrj.br.
Renato Santana
RS
Aguiar
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D045744:Cell Line, Tumor; D060085:Coinfection; D056906:Cyclin T / Q000378:metabolism; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics
C503684:CCNT1 protein, human; D056906:Cyclin T; D016356:Gene Products, tax; C514970:tax protein, Human T-lymphotrophic virus 1; D049452:Green Fluorescent Proteins; D042925:Positive Transcriptional Elongation Factor B; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9
HIV-1; HTLV-1; Latency; P-TEFb; Resting cells; Tax