Please use this identifier to cite or link to this item: http://repositorio.unifesp.br/handle/11600/28312
Title: Low accumulation of L90M in protease from subtype FHIV-1 with resistance to protease inhibitors is caused by the L89M polymorphism
Authors: Calazans, A.
Brindeiro, R.
Brindeiro, P.
Verli, H.
Arruda, M. B.
Gonzalez, LMF
Guimaraes, J. A.
Diaz, Ricardo Sobhie [UNIFESP]
Antunes, OAC
Tanuri, Amilcar [UNIFESP]
Universidade Federal do Rio de Janeiro (UFRJ)
Univ Fed Rio Grande Sul
Universidade Federal de São Paulo (UNIFESP)
Issue Date: 1-Jun-2005
Publisher: Univ Chicago Press
Citation: Journal of Infectious Diseases. Chicago: Univ Chicago Press, v. 191, n. 11, p. 1961-1970, 2005.
Abstract: 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.
URI: http://repositorio.unifesp.br/handle/11600/28312
ISSN: 0022-1899
Other Identifiers: http://dx.doi.org/10.1086/430002
Appears in Collections:Em verificação - Geral

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