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FUSION STAGE OF HIV-1 ENTRY DEPENDS ON VIRUS-INDUCED CELL SURFACE EXPOSURE OF PHOSPHATIDYLSERINE
- Publication Year :
- 2017
-
Abstract
- Summary HIV-1 entry into host cells starts with interactions between the viral envelope glycoprotein (Env) and cellular CD4 receptors and coreceptors. Previous work has suggested that efficient HIV entry also depends on intracellular signaling, but this remains controversial. Here we report that formation of the pre-fusion Env-CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the membrane lipid phosphatidylserine (PS). HIV-1-induced PS redistribution depends on Ca 2+ signaling triggered by Env-coreceptor interactions and involves the lipid scramblase TMEM16F. Externalized PS strongly promotes Env-mediated membrane fusion and HIV-1 infection. Blocking externalized PS or suppressing TMEM16F inhibited Env-mediated fusion. Exogenously added PS promoted fusion, with fusion dependence on PS being especially strong for cells with low surface density of coreceptors. These findings suggest that cell-surface PS acts as an important cofactor that promotes the fusogenic restructuring of pre-fusion complexes and likely focuses the infection on cells conducive to PS signaling.
- Subjects :
- 0301 basic medicine
Cell signaling
Phospholipid scramblase
viruses
Biology
Virus Replication
Microbiology
Article
03 medical and health sciences
chemistry.chemical_compound
Viral entry
Virology
Pliability
030102 biochemistry & molecular biology
Lipid bilayer fusion
virus diseases
Phosphatidylserine
Entry into host
Cell biology
030104 developmental biology
chemistry
Biochemistry
HIV-1
Parasitology
Cell activation
Intracellular
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....dcb952ca3f856014278de0174b6cdb58