Institute of Tropical Medicine Antwerp
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A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression

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Show simple item record Quiñones-Mateu, M. E. en_US Ball, S. C. en_US Marozsan, A. J. en_US Torre, V. S. en_US Albright, J. L. en_US Vanham, G. en_US van der Groen, G. en_US Colebunders, R. L. en_US Arts, E. J. en_US 2007-12-06T14:48:01Z 2007-12-06T14:48:01Z 2000 en_US
dc.identifier.issn 0022-538X en_US
dc.identifier.other ITG-M6A en_US
dc.identifier.other ITG-M7A en_US
dc.identifier.other ITG-C8A en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-IMMUN en_US
dc.identifier.other U-VIROL en_US
dc.identifier.other CLINIC en_US
dc.identifier.other U-HIVCLI en_US
dc.identifier.other JIF en_US
dc.identifier.other MULTI en_US
dc.identifier.other ABSTRACT en_US
dc.description.abstract This study was designed to examine the impact of human immunodeficiency virus type 1 (HIV-1) fitness on disease progression through the use of a dual competition/heteroduplex tracking assay (HTA). Despite numerous studies on the impact of HIV-1 diversity and HIV-specific immune response on disease progression, we still do not have a firm understanding of the long-term pathogenesis of this virus. Strong and early CD8-positive cytotoxic T-cell and CD4-positive T-helper cell responses directed toward HIV-infected cells appear to curb HIV pathogenesis. However, the rate at which the virus infects the CD4(+) T-cell population and possibly destroys the HIV-specific immune response may also alter the rate of disease progression. For HIV-1 fitness studies, we established conditions for dual HIV-1 infections of peripheral blood mononuclear cells (PBMC) and a sensitive HTA to measure relative virus production. A pairwise comparison was then performed to estimate the relative fitness of various non-syncytium-inducing/CCR5-tropic (NSI/R5) and syncytium-inducing/CXCR4-tropic (SI/X4) HIV-1 isolates. Four HIV-1 strains (two NSI/R5 and two SI/X4) with moderate ex vivo fitness were then selected as controls and competed against primary HIV-1 isolates from an HIV-infected Belgian cohort. HIV-1 isolates from long-term survivors (LTS) were outcompeted by control strains and were significantly less fit than HIV-1 isolates from patients with accelerated progression to AIDS (PRO). In addition, NSI/R5 HIV-1 isolates from PRO overgrew control SI/X4 strains, suggesting that not all SI/X4 HIV-1 isolates replicate more efficiently than all NSI/R5 isolates. Finally, there were strong, independent correlations between viral load and the total relative fitness values of HIV-1 isolates from PRO (r = 0.84, P = 0.033) and LTS (r = 0.86, P = 0.028). Separation of the PRO and LTS plots suggest that HIV-1 fitness together with viral load may be a strong predictor for the rate of disease progression. en_US
dc.language English en_US
dc.subject Viral diseases en_US
dc.subject HIV-1 en_US
dc.subject Assays en_US
dc.subject Disease progression en_US
dc.title A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression en_US
dc.type Article en_US
dc.citation.jtitle Journal of Virology en_US
dc.citation.volume 74 en_US
dc.citation.pages 9222-9233 en_US
dc.citation.jabbreviation J Virol en_US

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