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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: Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA. | Ristic and Chin Retrovirology 2010 7 73 http www.retrovirology.eom content 7 1 73 RETR0VIR0L0GY RESEARCH Open Access Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA Natalia Ristic Mario PS Chin Abstract Background The viral genome of HIV-1 contains several secondary structures that are important for regulating viral replication. The stem-loop 1 SL1 sequence in the 5 untranslated region directs HIV-1 genomic RNA dimerization and packaging into the virion. Without SL1 HIV-1 cannot replicate in human T cell lines. The replication restriction phenotype in the SL1 deletion mutant appears to be multifactorial with defects in viral RNA dimerization and packaging in producer cells as well as in reverse transcription of the viral RNA in infected cells. In this study we sought to characterize SL1 mutant replication restrictions and provide insights into the underlying mechanisms of compensation in revertants. Results HIV-1 lacking SL1 NLASL1 did not replicate in PM-1 cells until two independent non-synonymous mutations emerged G913A in the matrix domain E42K on day 18 postinfection and C1907T in the SP1 domain P10L on day 11 postinfection. NLASL1 revertants carrying either compensatory mutation showed enhanced infectivity in PM-1 cells. The SL1 revertants produced significantly more infectious particles per nanogram of p24 than did NLASL1. The SL1 deletion mutant packaged less HIV-1 genomic RNA and more cellular RNA particularly signal recognition particle RNA in the virion than the wild-type. NLASL1 also packaged 3- to 4-fold more spliced HIV mRNA into the virion potentially interfering with infectious virus production. In contrast both revertants encapsidated 2.5- to 5-fold less of these HIV-1 mRNA species. Quantitative RT-PCR analysis of RNA cross-linked with Gag in formaldehyde-fixed cells demonstrated that the compensatory mutations reduced the .