Estudo da relevância fisiológica da tioesterase humana II (hTE) na modulação de CD4 mediada pela proteína Nef do HIV 1

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

The down-modulation of CD4 receptor expression is one of the most important events during the HIV-1 infection. Among the three viral proteins involved in this process Nef, Env and Vpu, the first one is the most relevant. Results obtained by our group and others showed a clear relationship between the virus mediated receptor down-modulation, the increasing of infectivity and viral replication of HIV-1, suggesting a pathogenic role in this phenomenon and disease progression. More recently, we provided proof-of-concept that specific inhibition of Nef mediated CD4 down-modulation could be a good therapeutical strategy. Based on these results and aiming to identify new targets and therapeutical strategies, we investigated the physiological role of the human tioesterase II (hTE) in the down-modulation of CD4 receptor mediated by Nef. The hTE was described as one of the main cellular partners of Nef in this process. Using the interference RNA (RNAi) mechanism, as a molecular tool to block cellular and viral proteins expression involved in this phenomenon, we observed that hTE does not play a relevant role on Nef-CD4 modulation, as assigned by previous works. We showed here that the participation in the regulation of cellular surface CD4 levels possibly by a depalmitolation process, making the internalization independent of Nef. The hTE enzymatic action on Nef-NL43 transfected cells showed a probably synergism between Nef and hTE. The confirmation of these preliminary findings as well as, a more thoroughly understanding of the general biological consequences arising from the interaction between hTE and Nef, requires additional studies.

ASSUNTO(S)

aids cd4 down-modulation hiv-1 diminuição da expressão de cd4 hte e rnai aids medicina hte e rnai hiv-1 nef

ACESSO AO ARTIGO

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