ArticleRetrovirology2008
Evolution of DC-SIGN use revealed by fitness studies of R5 HIV-1 variants emerging during AIDS progression.
Article in Retrovirology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Evolution of Multiple Domains of the HIV-1 Envelope Glycoprotein during Coreceptor Switch with CCR5 Antagonist Therapy.Microbiology spectrum · 2022Trial
- Galectin-8 binds HIV envelope glycoproteins with high affinity and promotes viral infectivity.Frontiers in cellular and infection microbiology · 2026Article
- Reduced Baseline Sensitivity to Maraviroc Inhibition Among R5 HIV-1 Isolates From Individuals With Severe Immunodeficiency.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Review
- Mortality trends in the US Perinatal AIDS Collaborative Transmission Study (1986-2004).Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2011Article
- Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission.Human immunology · 2011Review
- Article
- An altered and more efficient mechanism of CCR5 engagement contributes to macrophage tropism of CCR5-using HIV-1 envelopes.Virology · 2010Article
- Variation in the biological properties of HIV-1 R5 envelopes: implications of envelope structure, transmission and pathogenesis.Future virology · 2010Article
- Lack of complex N-glycans on HIV-1 envelope glycoproteins preserves protein conformation and entry function.Virology · 2010Article
- Article
- The co-receptor signaling model of HIV-1 pathogenesis in peripheral CD4 T cells.Retrovirology · 2009Article
- How HIV changes its tropism: evolution and adaptation?Current opinion in HIV and AIDS · 2009Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAt early stages of infection CCR5 is the predominant HIV-1 coreceptor, but in approximately 50% of those infected CXCR4-using viruses emerge with disease progression. This coreceptor switch is correlated with an accelerated progression. However, those that maintain virus exclusively restricted to CCR5 (R5) also develop AIDS. We have previously reported that R5 variants in these "non-switch virus" patients evolve during disease progression towards a more replicative phenotype exhibiting altered CCR5 coreceptor interactions. DC-SIGN is a C-type lectin expressed by dendritic cells that HIV-1 may bind and utilize for enhanced infection of T cells in trans. To further explore the evolution of the R5 phenotype we analyzed sequential R5 isolates obtained before and after AIDS onset, i.e. at the chronic stage and during end-stage disease, with regard to efficiency of DC-SIGN use in trans-infections.
resultsResults from binding and trans-infection assays showed that R5 viruses emerging during end-stage AIDS disease displayed reduced ability to use DC-SIGN. To better understand viral determinants underlying altered DC-SIGN usage by R5 viruses, we cloned and sequenced the HIV-1 env gene. We found that end-stage R5 viruses lacked potential N-linked glycosylation sites (PNGS) in the gp120 V2 and V4 regions, which were present in the majority of the chronic stage R5 variants. One of these sites, amino acid position 160 (aa160) in the V2 region, also correlated with efficient use of DC-SIGN for binding and trans-infections. In fitness assays, where head-to-head competitions between chronic stage and AIDS R5 viruses were setup in parallel direct and DC-SIGN-mediated infections, results were further supported. Competitions revealed that R5 viruses obtained before AIDS onset, containing the V2 PNGS at aa160, were selected for in the trans-infection. Whereas, in agreement with our previous studies, the opposite was seen in direct target cell infections where end-stage viruses out-competed the chronic stage viruses.
conclusionResults of our study suggest R5 virus variants with diverse fitness for direct and DC-SIGN-mediated trans-infections evolve within infected individuals at end-stage disease. In addition, our results point to the importance of a glycosylation site within the gp120 V2 region for efficient DC-SIGN use of HIV-1 R5 viruses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.