The RNA genome of the lentivirus human immunodeficiency virus type 1 (HIV-1) is significantly richer in adenine nucleotides than the statistically equal distribution of the four different nucleotides that is expected. This compositional bias may be due to the guanine-to-adenine (G -->A) nucleotide hypermutation of the HIV genome, which has been explained by dCTP pool imbalances during reverse transcription. The adenine nucleotide bias together with the poor fidelity of HIV-1 reverse transcriptase markedly enhances the genetic variation of HIV and may be responsible for the rapid emergence of drug-resistant HIV-1 strains. We have now attempted to counteract the normal mutational pattern of HIV-1 in response to anti-HIV-1 drugs by altering the endogenous deoxynucleoside triphosphate pool ratios with antimetabolites in virus-infected cell cultures. We showed that administration of these antimetabolic compounds resulted in an altered drug resistance pattern due to the reversal of the predominant mutational flow of HIV (G -->A) to an adenine-to-guanine (A -->G) nucleotide pattern in the intact HIV-1-infected lymphocyte cultures. Forcing the virus to change its inherent nucleotide bias may lead to better control of viral drug resistance development.

Balzarini, J., Camarasa, M., Perez Perez, M., San Fleix, A., Velazquez, S., Perno, C.f., et al. (2001). Exploitation of the low fidelity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the nucleotide composition bias in the HIV-1 genome to alter the drug resistance development of HIV. JOURNAL OF VIROLOGY, 75(13), 5772-5777.

Exploitation of the low fidelity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the nucleotide composition bias in the HIV-1 genome to alter the drug resistance development of HIV

PERNO, CARLO FEDERICO;
2001-01-01

Abstract

The RNA genome of the lentivirus human immunodeficiency virus type 1 (HIV-1) is significantly richer in adenine nucleotides than the statistically equal distribution of the four different nucleotides that is expected. This compositional bias may be due to the guanine-to-adenine (G -->A) nucleotide hypermutation of the HIV genome, which has been explained by dCTP pool imbalances during reverse transcription. The adenine nucleotide bias together with the poor fidelity of HIV-1 reverse transcriptase markedly enhances the genetic variation of HIV and may be responsible for the rapid emergence of drug-resistant HIV-1 strains. We have now attempted to counteract the normal mutational pattern of HIV-1 in response to anti-HIV-1 drugs by altering the endogenous deoxynucleoside triphosphate pool ratios with antimetabolites in virus-infected cell cultures. We showed that administration of these antimetabolic compounds resulted in an altered drug resistance pattern due to the reversal of the predominant mutational flow of HIV (G -->A) to an adenine-to-guanine (A -->G) nucleotide pattern in the intact HIV-1-infected lymphocyte cultures. Forcing the virus to change its inherent nucleotide bias may lead to better control of viral drug resistance development.
2001
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
TSAO NUCLEOSIDE ANALOGS; G->A HYPERMUTATION; GENETIC-VARIATION; IN-VIVO; INHIBITORS; INFECTION; REPLICATION; HYDROXYUREA; ACID; SUBSTITUTIONS
6
Balzarini, J., Camarasa, M., Perez Perez, M., San Fleix, A., Velazquez, S., Perno, C.f., et al. (2001). Exploitation of the low fidelity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the nucleotide composition bias in the HIV-1 genome to alter the drug resistance development of HIV. JOURNAL OF VIROLOGY, 75(13), 5772-5777.
Balzarini, J; Camarasa, M; Perez Perez, M; San Fleix, A; Velazquez, S; Perno, Cf; De Clercq, E; Anderson, J; Karlsson, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/51566
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