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M94A0641.TXT
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1994-10-21
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Document 0641
DOCN M94A0641
TI Novel mutations associated with HIV-1 resistance to AZT.
DT 9412
AU Hooker DJ; Gurusinghe AD; Land SA; Birch CJ; McGavin C; Tachedjian G;
Deacon NJ; AIDS Molecular Biology Lab, NCHVR Macfarlane Burnet Cent.
for; Med. Res., Fairfield, Vic.
SO Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:63 (abstract no. TB4).
Unique Identifier : AIDSLINE ASHM5/94349014
AB Associated with AZT therapy is the emergence in patients of drug
resistant isolates of HIV-1. Certain mutations observed in the reverse
transcriptase (RT) gene/protein upon AZT therapy, namely at codons 41,
67, 70, 215 and 219, have previously been reported to contribute to AZT
resistance. By PCR amplification of patient PBL DNA and direct
sequencing of PCR products we have determined HIV-1 RT sequence of
AZT-sensitive and resistant isolate pairs, and of a series of isolates
taken from a single patient before, during and after AZT therapy. In
resistant isolates from pairs, mutations were seen at 41 and 215 but not
67, 70 or 219. In the sequential series mutations Glu44 to Asp and
Thr369 to lle correlated with drug therapy, as did previously reported
mutations at 41, 67, 70 and 215 but not 219. However one additional
mutation was observed in resistant isolates from all patients studied
here, namely Leu210 to Trp. Due to the consistent association of Trp210
with AZT resistance, we investigated its contribution by mutagenesis:
compared to wild-type HXB2, HXB2 mutated to Trp210 generated virus which
by IC50 was 3 fold more sensitive to AZT. Considering Trp210 has been
observed only with other mutations in these patients, we are now
examining its effect in conjunction with known resistance inducing
mutations.
DE Codon/GENETICS Drug Resistance, Microbial/GENETICS Human HIV
Infections/MICROBIOLOGY HIV-1/*DRUG EFFECTS/GENETICS
Mutation/*GENETICS Polymerase Chain Reaction Reverse
Transcriptase/ANTAGONISTS & INHIB/*GENETICS Zidovudine/*PHARMACOLOGY
MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).