Inhibition of ShcA isoforms p46/p52Shc enhances HIV-1 replication in CD4+ T-lymphocytes

HIV-1 infection decreases the number of CD4(+) T-cells, and apoptosis has been suggested among the mechanisms. Proteins of the Shc family are involved in a complex network of signal transcluction, differentiation, and apoptotic response to stress in many different cell types. Out of three homologous gene products (ShcA, ShcB, and ShcC, only two splicing variants of ShA are expressed in T-lymphocytes, namely p46Shc and p52Shc. In the present study, we report that inhibition of p46Shc and p52Shc by a dominant negative mutant enhances the yield of HIV-1 particles production without affecting efficiency of viral gene expression in CD4(+)-infected cells. The increase in HIV-1 replication in cells expressing the dominant negative mutant isoform ultimately correlates with a decrease in the percentage of cells entering apoptosis. The data presented suggest that ShcA proteins can play a role in committing CID4(+) T-cells to apoptosis, as a response to HIV-1 infection