Generation of intersubtype human immunodeficiency virus type 1 recombinants in env gene in vitro: Influences in the biological behavior and in the establishment of productive infections

Generation of intersubtype human immunodeficiency virus type 1 recombinants in env gene in vitro: Influences in the biological behavior and in the establishment of productive infections

Autor Costa, Luciana Jesus da Autor UNIFESP Google Scholar
Munerato, Patricia Autor UNIFESP Google Scholar
Diaz, Ricardo Sobhie Autor UNIFESP Google Scholar
Tanuri, A. Google Scholar
Instituição Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
Resumo The occurrence of human immunodeficiency virus type 1 (HIV-1) recombinant genomes belonging to different subtypes is a common event in regions where more than two subtypes cocirculate. Although there are accumulating data toward an increase in the number of intersubtype recombinants, little has been addressed about the biological behavior of such mosaic genomes. This work reports the biological characterization of engineered in vitro HIV-1 intersubtype recombinants in the gp120 region. the recombinants possess the entire gp120 of B or F Brazilian Isolates in the Z6 (subtype D) backbone. Hers we show that this type of recombinant structure results in profound impairment to the establishment of productive infections in CD4-positive cells. the characterization of biological properties of those recombinant viruses demonstrated viral production occurring only during a transient peak early on infection and that they are not able to down-regulate the expression of CD4 receptor on the cell surface. We also report the phenotype reversion of one recombinant virus studied here, after 62 days in culture. Two amino acid substitutions in highly constant gp120 regions (C1 and C4) were identified in the revertant virus. the mutation occurring in the C4 region is localized near two amino acid residues critical for gp120/CD4 interaction. Based on these data, we suggest that failure in CD4 down-modulation by recombinant viruses can be due to a structural dysfunction of gp160 protein unable to block CD4 at the endoplasmic reticule. the possibilities that the establishment of latent infections can be directly related to the continuous expression of CD4 on the infected cell surface and that the occurrence of mutations in amino acid nearby residues critical for gp120/CD4 interaction can restore the fully productive infectious process are discussed. (C) 2000 Academic Press.
Idioma Inglês
Data de publicação 2000-03-15
Publicado em Virology. San Diego: Academic Press Inc, v. 268, n. 2, p. 440-451, 2000.
ISSN 0042-6822 (Sherpa/Romeo, fator de impacto)
Publicador Academic Press Inc
Extensão 440-451
Fonte http://dx.doi.org/10.1006/viro.1999.0133
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000086029000024
Endereço permanente http://repositorio.unifesp.br/handle/11600/26271

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