INVESTIGADORES
REY Osvaldo
artículos
Título:
HIV type 1 Gag and nucleocapsid proteins: cytoskeletal localization and effects on cell motility
Autor/es:
IBARRONDO FJ, CHOI R, GENG YZ, CANON J, REY O, BALDWIN GC, KROGSTAD P.
Revista:
AIDS RESEARCH AND HUMAN RETROVIRUSES
Editorial:
MARY ANN LIEBERT INC
Referencias:
Año: 2001 p. 1489 - 14500
ISSN:
0889-2229
Resumen:
Cell motility is likely to play a pivotal role in HIV infection by
promoting the dissemination of infected cells. On the basis of
observations indicating an interaction between HIV-1 Gag and target
cell filamentous actin, we hypothesized that these interactions would
promote cell motility of HIV-infected cells. Indeed, we have found that
HIV-1 infection enhances the chemotactic response of macrophages. To
specifically investigate the significance of the interactions between
Gag and cellular actin, we transfected NIH 3T3 fibroblasts and HeLa
cells with a construct that permits the expression of HIV-1 Gag in the
absence of any other viral protein. Fractionation experiments showed
that Gag was present in cytoskeletal fraction containing long actin
filaments and in a high-speed postcytoskeletal fraction with short
actin filaments. We have also localized HIV-1 Gag to the lamellipodia
of chemoattractant-stimulated cells. Significantly, the motility of
Gag-expressing cells was enhanced in chemotaxis assays. In vitro
mutagenesis experiments showed that HIV-1 Gag binds filamentous actin
through the nucleocapsid domain (NC). An NC-green fluorescent protein
fusion had the same cellular distribution as the complete protein, and
its expression increased cell motility. These data suggest that
interactions between HIV-1 Gag and actin in infected cells enhance cell
motility. Ultimately this enhanced motility of infected cells could
promote the dissemination of virus into the brain and other tissues.