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J Virol, May 1998, p. 3520-3523, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Switch to Unusual Amino Acids at Codon 215 of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Gene in Seroconvertors Infected with Zidovudine-Resistant Variants

Sabine Yerly,1 Abdelrahim Rakik,1 Sabine Kinloch De Loes,1 Bernard Hirschel,2 Diane Descamps,3 Françoise Brun-Vézinet,3 and Luc Perrin1,*

Laboratory of Virology1 and AIDS Center,2 Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland, and Laboratory of Virology, Bichat-Claude Bernard Hospital, Paris, France3

Received 20 August 1997/Accepted 15 January 1998

Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in successive plasma samples from eight seroconverting patients infected with virus bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV) resistance. At baseline, additional mutations associated with ZDV resistance were detected. Three patients had the M41L amino acid change, which persisted. Two patients had both the D67N and the K70R amino acid substitutions; reversion to the wild type was seen at both positions in one of these patients and at codon 70 in the other one. Reversion to the wild type at codon 215 was observed in only one of eight patients. Unusual amino acids, such as aspartic acid (D) and cysteine (C), appeared at position 215 in four patients during follow-up. These variants isolated by coculturing were sensitive to ZDV. Overgrowth of these variants suggests that they have better fitness than the original T215Y variant. Intraindividual nucleoside substitutions over time were 10 times more frequent in codons associated with ZDV resistance (41, 67, 70, 215, and 219) than in other codons of the RT domain. The predominance of nonsynonymous substitutions observed over time suggests that most changes reflect adaptation of the RT function. The variance in sequence evolution observed among patients, in particular at codon 215, supports a role for chance in the evolution of the RT domain.

* Corresponding author. Mailing address: Laboratory of Virology, Geneva University Hospital, 1211 Geneva 14, Switzerland. Phone: 41-22-37 24 991. Fax: 41-22-37 24 990. E-mail: luc.perrin{at}hcuge.ch.

J Virol, May 1998, p. 3520-3523, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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