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Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness.
van der Kuyl, Antoinette C; Kozaczynska, Karolina; Ariën, Kevin K; Gali, Youssef; Balázs, Victoria R; Dekker, Stefan J; Zorgdrager, Fokla; Vanham, Guido; Berkhout, Ben; Cornelissen, Marion.
Afiliación
  • van der Kuyl AC; Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. a.c.vanderkuyl@amc.uva.nl
Retrovirology ; 7: 60, 2010 Jul 20.
Article en En | MEDLINE | ID: mdl-20646276
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, 4769-73). 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. In a luciferase assay, only the LTR from the primary virus of patient P had lower transcriptional activity compared with the superinfecting virus.

CONCLUSIONS:

These preliminary findings suggest the interesting scenario that superinfection occurs preferentially in patients infected with a relatively attenuated HIV-1 isolate.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / Sobreinfección / Infecciones por VIH / VIH-1 Tipo de estudio: Health_technology_assessment / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Retrovirology Asunto de la revista: VIROLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / Sobreinfección / Infecciones por VIH / VIH-1 Tipo de estudio: Health_technology_assessment / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Retrovirology Asunto de la revista: VIROLOGIA Año: 2010 Tipo del documento: Article País de afiliación: Países Bajos