Nucleic Acids Research, Vol 26, Issue 24 5692-5698, Copyright © 1998 by Oxford University Press
Y Quan, C Liang, P Inouye and MA Wainberg
We have studied the relationship between the length of HIV-1 reverse
transcriptase (RT)-mediated nucleotide polymerization and inhibitors of
these reactions in cell-free RT assays performed in the presence of either
of two dideoxynucleoside triphosphates (ddNTPs), i.e. AZTTP or 3TCTP, or
nevirapine, a non-nucleoside RT inhibitor. These reactions employed a
heterologous RNA template and three DNA oligonucleotide primers, i.e. pAR,
dPR and PA, that yielded distinct full-length products of 65, 192 and 376
nt, respectively, in the absence of inhibitor. We now show that the extent
of inhibition of RT activity was greatest with use of the PA primer, which
normally yielded the longest reaction product, and that lesser degrees of
inhibition were noted in the reactions that generated shorter products. For
example, at a concentration of 5 microM AZTTP, the extent of inhibition was
75% with the PA primer but only 40% and <10% when reactions were primed
by the dPR and pAR primers, respectively. Similar results were obtained
when either a mutated form of HIV RT (i.e. M184V), associated with
resistance to 3TC, was tested in the presence of 3TCTP or when RT derived
from Moloney murine leukemia virus (M-MuLV) was tested in the presence of
AZTTP.
ARTICLES
Enhanced impairment of chain elongation by inhibitors of HIV reverse transcriptase in cell-free reactions yielding longer DNA products
McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
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