ArticlePLoS pathogens2022
A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 6 citations in OpenAlex.
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- Dynamics of natural and pharmacologic control of an SIV variant with an envelope trafficking defect.The Journal of experimental medicine · 2026Article
- Depletion and recovery of IgG following treatment with an anti-FcRn antibody and IdeS in pigtail macaques.Clinical and experimental immunology · 2026Article
- Depletion and recovery of IgG following treatment with Rozanoliximab and Imlifidase in pigtail macaques.bioRxiv : the preprint server for biology · 2025Article
- Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors.Science advances · 2024Article
- Biphasic decay of intact SHIV genomes following initiation of antiretroviral therapy complicates analysis of interventions targeting the reservoir.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Rab11-FIP1C Is Dispensable for HIV-1 Replication in Primary CD4Journal of virology · 2022Article
- Viral and Host Factors Regulating HIV-1 Envelope Protein Trafficking and Particle Incorporation.Viruses · 2022Review
Corrections and comments
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Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
Abstract
The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734-736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo.
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