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: Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly. | Votteler et al. Retrovirology 2011 8 11 http content 8 1 11 RETROVIROLOGY RESEARCH Open Access Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly 1 t 1 t 1 1 1 1 Jorg Votteler Liane Neumann Sabine Hahn Friedrich Hahn Pia Rauch Kerstin Schmidt 1 2 2 3 4 5 Nicole Studtrucker Sara M0 Solbak Torgils Fossen Peter Henklein David E Ott Gudrun Holland Norbert Bannert5 Ulrich Schubert1 Abstract Background The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly L- domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene the 52 amino acid peptide binds at least to two cellular budding factors Tsg101 and ALIX is a substrate for phosphorylation ubiquitination and sumoylation and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected known functional domains mostly overlap with several conserved residues in p6. In this study we investigated the importance of the highly conserved serine residue at position 40 which until now has not been assigned to any known function of p6. Results Consistently with previous data we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However the only feasible S40F mutation that preserves the overlapping pol open reading frame ORF reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly L-domain mediated virus release is not dependent on the integrity of Ser-40. However the S40F mutation significantly reduces the specific infectivity of released virions. Further it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid CA and the spacer peptide SP1 in Gag without affecting cleavage of other Gag products. This deficiency in processing of CA in consequence led to an irregular morphology
