Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice | Garg et al. Virology Journal 2011 8 34 http content 8 1 34 J VIROLOGY JOURNAL RESEARCH Open Access Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice 1 1 1 Himanshu Garg Anjali Joshi Chunting Ye Premlata Shankar N Manjunath Abstract Background The mechanism by which HIV infection leads to a selective depletion of CD4 cells leading to immunodeficiency remains highly debated. Whether the loss of CD4 cells is a direct consequence of virus infection or bystander apoptosis of uninfected cells is also uncertain. Results We have addressed this issue in the humanized mouse model of HIV infection using a HIV variant with a point mutation in the gp41 region of the Env glycoprotein that alters its fusogenic activity. We demonstrate here that a single amino acid change V38E altering the cell-to-cell fusion activity of the Env minimizes CD4 loss in humanized mice without altering viral replication. This differential pathogenesis was associated with a lack of bystander apoptosis induction by V38E virus even in the presence of similar levels of infected cells. Interestingly immune activation was observed with both WT and V38E infection suggesting that the two phenomena are likely not interdependent in the mouse model. Conclusions We conclude that Env fusion activity is one of the determinants of HIV pathogenesis and it may be possible to attenuate HIV by targeting gp41. Introduction HIV infection in humans leads to a selective depletion of CD4 T cells that culminates in immunodeficiency or AIDS. While it is clear that the loss of CD4 T cells is initiated by HIV infection the mechanism behind this phenomenon remains highly debated. CD4 T cell loss can occur due to multiple mechanisms direct killing of infected cells 1 indirect killing of uninfected cells 2 a defect in the capacity for lymphocyte proliferation or turnover or both 3 and or an overzealous chronic immune response and immune activation
