Recombinant human antibodies against the reverse transcriptase of human immunodeficiency virus type-1

Alon Herschhorn, Arie Admon, Amnon Hizi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Inhibitory antibodies to the reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) can be used to block the life cycle of the virus. We have isolated five different human single chain Fv (ScFv) antibodies specific for HIV-1 RT from an antibody phage display library. Three of these antibodies inhibited the RNA-dependent DNA polymerase (RDDP) activity of RT and one of the three (F-6) inhibited also its DNA-dependent DNA polymerase (DDDP) activity. Unexpectedly, F-6 binds to the carboxyl terminus of the large subunit of RT, which contains the ribonuclease H (RNase H) domain, and not the polymerase domain of the protein. Moreover, this binding did not inhibit the RNase H enzymatic activity. To further characterize F-6 antibody, two cyclic synthetic peptides based on the amino acids sequences of the CDR3 of F-6 were synthesized. Peptide F-6CDRH3, with the sequence of CDR3 of the heavy chain, inhibited the RDDP activity of RT while peptide F-6CDRL3, with the sequence of CDR3 of the light chain, had no effect on this activity of RT. These results indicate that some of the effects of F-6 are mediated by the CDR3 of the heavy chain. The antibodies identified here will be further tested as intrabodies for their capacity to protect human cells from HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)154-163
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1648
Issue number1-2
DOIs
StatePublished - May 30 2003

Keywords

  • Inhibition of enzymatic activity
  • Phage display
  • ScFv antibody

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