Studies of neutralizing monoclonal antibody to human immunodeficiency virus type 1 reverse transcriptase: antagonistic and synergistic effects in reactions performed in the presence of nucleoside and nonnucleoside inhibitors, respectively.
We have assessed interactions between the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) and a neutralizing monoclonal antibody (1E8) that hinders binding of deoxynucleoside triphosphate (dNTP) substrates. Steady-state reactions with homopolymeric template-primers revealed that 1E8 antagonized inhibition of RT activity mediated by 3'-azido-3'-deoxythymidine triphosphate and 2',3'-dideoxycytidine triphosphate. However, an additive or synergistic inhibition of RT polymerase activity was noted when 1E8 and the nonnucleoside RT inhibitors nevirapine and delavirdine were studied. Chain elongation and dNTP incorporation studies using an HIV-1 genome-derived heteropolymeric template and either oligodeoxynucleotide or tRNA3(Lys) as the primer yielded results consistent with the above observations. 1E8 also increased pausing at certain sites during synthesis of negative-strand, strong-stop DNA, whether or not ddNTP and nonnucleoside RT inhibitors were present.
Gu
Z
Z
McGill University AIDS Centre, McGill University, Montreal, Quebec, Canada.
Li
X
X
Quan
Y
Y
Parniak
M A
MA
Wainberg
M A
MA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D020008:Delavirdine; D003845:Deoxycytosine Nucleotides / Q000494:pharmacology; D054306:Dideoxynucleotides; D015483:HIV Antibodies / Q000276:immunology*; D054303:HIV Reverse Transcriptase; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D009500:Neutralization Tests; D019829:Nevirapine; D010441:Peptide Chain Elongation, Translational; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects / Q000276:immunology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013942:Thymine Nucleotides / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D003845:Deoxycytosine Nucleotides; D054306:Dideoxynucleotides; D015483:HIV Antibodies; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; D015215:Zidovudine; C037406:2',3'-dideoxycytidine 5'-triphosphate; C052873:zidovudine triphosphate; D004247:DNA; D019829:Nevirapine; D020008:Delavirdine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase