tailieunhanh - Báo cáo y học: "Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitnesc"

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: Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness. | van der Kuyl et al. Retrovirology 2010 7 60 http content 7 1 60 RETR0VIR0L0GY RESEARCH Open Access Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness 1 2 1 Antoinette C van der Kuyl Karolina Kozaczynska 1 Kevin K Arien Youssef Gali Victoria R Balazs Stefan J Dekker1 Fokla Zorgdrager1 Guido Vanham2 4 Ben Berkhout1 Marion Cornelissen1 Abstract Background Two HIV-1 positive patients L and P participating in the Amsterdam Cohort studies acquired an HIV-1 superinfection within half a year from their primary HIV-1 infection Jurriaans et al. JAIDS 2008 47 69-73 . The aim of this study was to compare the replicative fitness of the primary and superinfecting HIV-1 strains of both patients. The use of isolate-specific primer sets indicated that the primary and secondary strains co-exist in plasma at all time points after the moment of superinfection. Results Biological HIV-1 clones were derived from peripheral blood CD4 T cells at different time point and identified as the primary or secondary virus through sequence analysis. Replication competition assays were performed with selected virus pairs in PHA IL-2 activated peripheral blood mononuclear cells PBMC s and analyzed with the Heteroduplex Tracking Assay HTA and isolate-specific PCR amplification. In both cases we found a replicative advantage of the secondary HIV-1 strain over the primary virus. Full-length HIV-1 genomes were sequenced to find possible explanations for the difference in replication capacity. Mutations that could negatively affect viral replication were identified in the primary infecting strains. In patient L the primary strain has two insertions in the LTR promoter combined with a mutation in the tat gene that has been associated with decreased replication capacity. The primary HIV-1 strain isolated from patient P has two mutations in the LTR that have been associated with a reduced replication rate.