Benetti Luca, Calistri Arianna, Ulivieri Cristina, Cabrelle Anna, Baldari Cosima T, Palù Giorgio, Parolin Cristina
Department of Histology, Microbiology and Medical Biotechnologies, Section of Microbiology and Virology, University of Padua, Padua, Italy.
J Cell Physiol. 2004 Apr;199(1):40-6. doi: 10.1002/jcp.10449.
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.
HIV-1感染会减少CD4(+) T细胞的数量，并且细胞凋亡被认为是其中的机制之一。Shc家族的蛋白质参与了许多不同细胞类型中复杂的信号转导、分化以及对应激的凋亡反应网络。在三个同源基因产物（ShcA、ShcB和ShcC）中，只有ShcA的两个剪接变体在T淋巴细胞中表达，即p46Shc和p52Shc。在本研究中，我们报告称，通过显性负性突变体抑制p46Shc和p52Shc可提高HIV-1颗粒的产生量，而不影响CD4(+)感染细胞中病毒基因表达的效率。表达显性负性突变体异构体的细胞中HIV-1复制的增加最终与进入凋亡的细胞百分比的降低相关。所呈现的数据表明，作为对HIV-1感染的反应，ShcA蛋白可能在促使CD4(+) T细胞凋亡中发挥作用。
