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 transduction, 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 CD4(+) T-cells to apoptosis, as a response to HIV-1 infection.
Department of Histology, Microbiology and Medical Biotechnologies, Section of Microbiology and Virology, University of Padua, Padua, Italy.
Luca
L
Benetti
Arianna
A
Calistri
Cristina
C
Ulivieri
Anna
A
Cabrelle
Cosima T
CT
Baldari
Giorgio
G
Palù
Cristina
C
Parolin
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D015658:HIV Infections; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D019169:Jurkat Cells; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014779:Virus Replication / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D016877:Oxidants; D020033:Protein Isoforms; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D006861:Hydrogen Peroxide