Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity. | Bhakta et al. Retrovirology 2011 8 37 http content 8 1 37 RETR0VIR0L0GY RESEARCH Open Access Mutagenesis of tyrosine and di-leucine motifs in the HIV-1 envelope cytoplasmic domain results in a loss of Env-mediated fusion and infectivity Sushma J Bhakta Liang Shangf Jessica L Prince Daniel T Claiborne and Eric Hunter Abstract Background The gp41 component of the Human Immunodeficiency Virus HIV envelope glycoprotein Env contains a long cytoplasmic domain CD with multiple highly conserved tyrosine Y and dileucine LL motifs. Studies suggest that the motifs distal to major endocytosis motif Y712HRL located at residues 712-715 of Env may contribute to Env functionality in the viral life cycle. In order to examine the biological contribution of these motifs in the biosynthesis transport and function of Env we constructed two panels of mutants in which the conserved Y- and LL-motifs were sequentially substituted by alternative residues either in the presence or absence of Y712. Additional mutants targeting individual motifs were then constructed. Results All mutant Envs when expressed in the absence of other viral proteins maintained at least WT levels of Env surface staining by multiple antibodies. The Y712 mutation Y712C contributed to at least a 4-fold increase in surface expression for all mutants containing this change. Sequential mutagenesis of the Y- and LL-motifs resulted in a generally progressive decrease in Env fusogenicity. However additive mutation of dileucine and tyrosine motifs beyond the tyrosine at residue 768 resulted in the most dramatic effects on Env incorporation into virions viral infectivity and virus fusion with target cells. Conclusions From the studies reported here we show that mutations of the Y- and LL-motifs which effectively eliminate the amphipathic nature of the lytic peptide 2 LLP2 domain or disrupt YW and LL motifs in a region spanning residues 795-803 YWWNLLQYW just C-terminal of LLP2 can dramatically interfere .
