ArticleJournal of virology2009
The heptad repeat 2 domain is a major determinant for enhanced human immunodeficiency virus type 1 (HIV-1) fusion and pathogenicity of a highly pathogenic HIV-1 Env.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Short Communication: A Recombinant Variant with Increased Envelope Entry Efficiency Emerged During Early Infection of an HIV-1 Subtype C Dual Infected Rapid Progressor.AIDS research and human retroviruses · 2016Trial
- Article
- The Interplay of HIV and Autophagy in Early Infection.Frontiers in microbiology · 2021Review
- Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors.Viruses · 2020Article
- Identification of HIV-1 Envelope Mutations that Enhance Entry Using Macaque CD4 and CCR5.Viruses · 2020Article
- Differential Pathogenicity of SHIV KB9 and 89.6 Env Correlates with Bystander Apoptosis Induction in CD4+ T cells.Viruses · 2019Article
- Article
- Low levels of HIV-1 envelope-mediated fusion are associated with long-term survival of an infected CCR5-/- patient.AIDS (London, England) · 2018Article
- Review
- Genetic Pathway of HIV-1 Resistance to Novel Fusion Inhibitors Targeting the Gp41 Pocket.Journal of virology · 2015Article
- Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell depletion.The Journal of clinical investigation · 2015Article
- HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms.Journal of virology · 2015Article
- Mechanism of HIV-1 Resistance to Short-Peptide Fusion Inhibitors Targeting the Gp41 Pocket.Journal of virology · 2015Article
- Viral envelope is a major determinant of enhanced fitness of a multidrug-resistant HIV-1 variant.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice.PLoS pathogens · 2014Article
- A rationally engineered anti-HIV peptide fusion inhibitor with greatly reduced immunogenicity.Antimicrobial agents and chemotherapy · 2013Article
- Resistance of human immunodeficiency virus type 1 to a third-generation fusion inhibitor requires multiple mutations in gp41 and is accompanied by a dramatic loss of gp41 function.Journal of virology · 2011Article
- Type I interferon contributes to CD4+ T cell depletion induced by infection with HIV-1 in the human thymus.Journal of virology · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Human immunodeficiency virus type 1 (HIV-1)-mediated depletion of CD4+ lymphocytes in an infected individual is the hallmark of progression to AIDS. However, the mechanism for this depletion remains unclear. To identify mechanisms of HIV-1-mediated CD4 T-cell death, two similar viral isolates obtained from a rapid progressor patient with significantly different pathogenic phenotypes were studied. One isolate (R3A) demonstrates enhanced pathogenesis in both in vivo models and relevant ex vivo lymphoid organ model systems compared to another isolate, R3B. The pathogenic determinants were previously mapped to the V5-gp41 envelope region, correlating functionally with enhanced fusion activity and elevated CXCR4 binding affinity. To further elucidate specific differences between R3A and R3B within the V5-gp41 domains that enhance CD4 depletion, R3A-R3B chimeras to study the V5-gp41 region were developed. Our data demonstrate that six residues in the ectodomain of R3A provide the major determinant for both enhanced Env-cell fusion and pathogenicity. Furthermore, three amino acid differences in the heptad repeat 2 (HR-2) domain of R3A determined its fusion activity and significantly elevated its pathogenic activity. The chimeric viruses with enhanced fusion activity, but not elevated CXCR4 affinity, correlated with high pathogenicity in the thymus organ. We conclude that the functional domain of a highly pathogenic HIV-1 Env is determined by mutations in the HR-2 region that contribute to enhanced fusion and CD4 T-cell depletion.
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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.