Endosomal Trafficking of HIV-1 Gag and Genomic RNAs Regulates Viral Egress*
AUTOR(ES)
Molle, Dorothée
FONTE
American Society for Biochemistry and Molecular Biology
RESUMO
HIV-1 Gag can assemble and generate virions at the plasma membrane, but it is also present in endosomes where its role remains incompletely characterized. Here, we show that HIV-1 RNAs and Gag are transported on endosomal vesicles positive for TiVamp, a v-SNARE involved in fusion events with the plasma membrane. Inhibition of endosomal traffic did not prevent viral release. However, inhibiting lysosomal degradation induced an accumulation of Gag in endosomes and increased viral production 7-fold, indicating that transport of Gag to lysosomes negatively regulates budding. This also suggested that endosomal Gag-RNA complexes could access retrograde pathways to the cell surface and indeed, depleting cells of TiVamp-reduced viral production. Moreover, inhibition of endosomal transport prevented the accumulation of Gag at sites of cellular contact. HIV-1 Gag could thus generate virions using two pathways, either directly from the plasma membrane or through an endosome-dependent route. Endosomal Gag-RNA complexes may be delivered at specific sites to facilitate cell-to-cell viral transmission.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2740597Documentos Relacionados
- A myristoyl switch regulates membrane binding of HIV-1 Gag
- Imaging the interaction of HIV-1 genomes and Gag during assembly of individual viral particles
- Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane
- HIV-1 Gag Processing Intermediates Trans-dominantly Interfere with HIV-1 Infectivity*
- Similarity in env and gag genes between genomic RNAs of human immunodeficiency virus type 1 (HIV-1) from mother and infant is unrelated to time of HIV-1 RNA positivity in the child.