High sequence conservation of human immunodeficiency virus type 1 reverse transcriptase under drug pressure despite the continuous appearance of mutations
- CECCHERINI SILBERSTEIN, FRANCESCA
- SANTORO, MARIA
- SVICHER, VALENTINA
- PERNO, CARLO FEDERICO
- Gago, F
- Gori, C
- Rodríguez Barrios, F
- d'Arrigo, R
- Ciccozzi, M
- BERTOLI, ADA
- d'Arminio Monforte, A
- Balzarini, J
- Antinori, A
DOIAbstract
To define the extent of sequence conservation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) in vivo, the first 320 amino acids of RT obtained from 2,236 plasma-derived samples from a well-defined cohort of 1,704 HIV-1-infected individuals (457 drug naïve and 1,247 drug treated) were analyzed and examined in structural terms. In naïve patients, 233 out of these 320 residues (73%) were conserved (<1% variability). The majority of invariant amino acids clustered into defined regions comprising between 5 and 29 consecutive residues. Of the nine longest invariant regions identified, some contained residues and domains critical for enzyme stability and function. In patients treated with RT inhibitors, despite profound ...
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