Low accumulation of L90M in protease from subtype FHIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism

Low accumulation of L90M in protease from subtype FHIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism

Autor Calazans, A. Google Scholar
Brindeiro, R. Google Scholar
Brindeiro, P. Google Scholar
Verli, H. Google Scholar
Arruda, M. B. Google Scholar
Gonzalez, LMF Google Scholar
Guimaraes, J. A. Google Scholar
Diaz, Ricardo Sobhie Autor UNIFESP Google Scholar
Antunes, OAC Google Scholar
Tanuri, Amilcar Autor UNIFESP Google Scholar
Instituição Universidade Federal do Rio de Janeiro (UFRJ)
Univ Fed Rio Grande Sul
Universidade Federal de São Paulo (UNIFESP)
Resumo Background. This work evaluates the role of subtype F human immunodeficiency virus type 1 (HIV-1) protease ( PR) substitutions L89M and L90M in viral replication and resistance to PR inhibitors (PIs).Methods. Subtype B and F PR genes were subjected to site-directed mutagenesis, to create and reverse the methionine at positions 89 and 90. Viruses were re-created in cell culture, and their replicative capacity was assessed by fitness assay. Generated viruses were also phenotyped for PI resistance.Results. the subtype F clone (89M90L) showed a replicative capacity comparable to that of the PI-susceptible subtype B clone (89L90L) and was more fit than the L89M mutated subtype B clone ( 89M90L). Both 89M90M subtype B and F clones presented the lowest fitness s values. the L89M mutation impacted phenotypic resistance to all PIs in half of the subtype F isolates but not in the subtype B isolates. Subtype F isolates presented a phenotypic profile similar to that of subtype B isolates when the M89L mutation was introduced.Conclusion. the L89M mutation in subtype F viruses is a high genetic barrier to the accumulation of the L90M resistance mutation and can function as a resistance mutation, depending on the presence of other polymorphisms in the subtype F PR backbone.
Idioma Inglês
Data de publicação 2005-06-01
Publicado em Journal of Infectious Diseases. Chicago: Univ Chicago Press, v. 191, n. 11, p. 1961-1970, 2005.
ISSN 0022-1899 (Sherpa/Romeo, fator de impacto)
Publicador Univ Chicago Press
Extensão 1961-1970
Fonte http://dx.doi.org/10.1086/430002
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000228881100024
Endereço permanente http://repositorio.unifesp.br/handle/11600/28312

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