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Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness
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...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918528/ https://www.ncbi.nlm.nih.gov/pubmed/20646276 http://dx.doi.org/10.1186/1742-4690-7-60 |
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author | 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 |
author_facet | 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 |
author_sort | van der Kuyl, Antoinette C |
collection | PubMed |
description | 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. 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. |
format | Text |
id | pubmed-2918528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29185282010-08-10 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 Retrovirology Research 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. 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. BioMed Central 2010-07-20 /pmc/articles/PMC2918528/ /pubmed/20646276 http://dx.doi.org/10.1186/1742-4690-7-60 Text en Copyright ©2010 van der Kuyl et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research 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 Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness |
title | Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness |
title_full | Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness |
title_fullStr | Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness |
title_full_unstemmed | Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness |
title_short | Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness |
title_sort | analysis of infectious virus clones from two hiv-1 superinfection cases suggests that the primary strains have lower fitness |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918528/ https://www.ncbi.nlm.nih.gov/pubmed/20646276 http://dx.doi.org/10.1186/1742-4690-7-60 |
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