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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model
Retrovirology, Volume 11, No. 1, Article 113, Year 2014
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Description
Background: Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns. Results: In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5+ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5+ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs. Conclusions: Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals. © 2014 Pingen et al.; licensee BioMed Central Ltd.
Authors & Co-Authors
Wensing, Annemarie Marie J.
Netherlands, Utrecht
University Medical Center Utrecht
van Ham, Petra Maria
Netherlands, Utrecht
University Medical Center Utrecht
Boucher, Charles A.B.
Netherlands, Rotterdam
Erasmus Mc
Geijtenbeek, Teunis B.H.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Nijhuis, Monique M.Oude
Netherlands, Utrecht
University Medical Center Utrecht
Statistics
Citations: 9
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1186/s12977-014-0113-9
ISSN:
17424690
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study