| Autor: |
Amara A; Unité d'Immunologie Virale, Institut Pasteur, F-75724 Paris Cedex 15, France. aamara@pasteur.fr, Vidy A, Boulla G, Mollier K, Garcia-Perez J, Alcamí J, Blanpain C, Parmentier M, Virelizier JL, Charneau P, Arenzana-Seisdedos F |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of virology [J Virol] 2003 Feb; Vol. 77 (4), pp. 2550-8. |
| DOI: |
10.1128/jvi.77.4.2550-2558.2003 |
| Abstrakt: |
The requirement of human immunodeficiency virus (HIV)-induced CCR5 activation for infection by R5 HIV type 1 (HIV-1) strains remains controversial. Ectopic CCR5 expression in CD4(+)-transformed cells or pharmacological inhibition of G(alpha)i proteins coupled to CCR5 left unsolved whether CCR5-dependent cell activation is necessary for the HIV life cycle. In this study, we investigated the role played by HIV-induced CCR5-dependent cell signaling during infection of primary CD4-expressing leukocytes. Using lentiviral vectors, we restored CCR5 expression in T lymphocytes and macrophages from individuals carrying the homozygous 32-bp deletion of the CCR5 gene (ccr5 Delta32/Delta32). Expression of wild-type (wt) CCR5 in ccr5 Delta32/Delta32 cells permitted infection by R5 HIV isolates. We assessed the capacity of a CCR5 derivative carrying a mutated DRY motif (CCR5-R126N) in the second intracellular loop to work as an HIV-1 coreceptor. The R126N mutation is known to disable G protein coupling and agonist-induced signal transduction through CCR5 and other G protein-coupled receptors. Despite its inability to promote either intracellular calcium mobilization or cell chemotaxis, the inactive CCR5-R126N mutant provided full coreceptor function to several R5 HIV-1 isolates in primary cells as efficiently as wt CCR5. We conclude that in a primary, CCR5-reconstituted CD4(+) cell environment, G protein signaling is dispensable for R5 HIV-1 isolates to actively infect primary CD4(+) T lymphocytes or macrophages. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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