Abstract
BackgroundTwo 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.ResultsBiological 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. In a luciferase assay, only the LTR from the primary virus of patient P had lower transcriptional activity compared with the superinfecting virus.ConclusionsThese preliminary findings suggest the interesting scenario that superinfection occurs preferentially in patients infected with a relatively attenuated HIV-1 isolate.
Highlights
Two HIV-1 positive patients, L and P, participating in the Amsterdam Cohort studies acquired an HIV1 superinfection within half a year from their primary HIV-1 infection (Jurriaans et al, JAIDS 2008, 47:69-73)
Viral fitness is the parameter that is defined by the ability of an individual genotype to produce infectious progeny in a specific environment [1,2], and it can be divided into transmission fitness, replicative fitness or immune-evasion fitness
Two multidrug-resistant HIV-1 strains were involved, of which the first appeared more fit in competition assays
Summary
Two HIV-1 positive patients, L and P, participating in the Amsterdam Cohort studies acquired an HIV1 superinfection within half a year from their primary HIV-1 infection (Jurriaans et al, JAIDS 2008, 47:69-73). Two studies compared the relative fitness of the superinfecting strain with that of the primary strain in replication assays, but the analysis was restricted to the contribution of the pol gene [16,17]. In both cases no differences were observed, suggesting that fitness determining factors may be located elsewhere in the viral genome, as the superinfecting strains appeared to be more fit in vivo. Full genome sequences of the viral clones were investigated to detect mutations that could explain the observed differences in replication capacity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
