A nucleotide substitution in the tRNALys primer binding site dramatically increases replication of recombinant simian immunodeficiency virus containing a human immunodeficiency virus type 1 reverse transcriptase

Kelly Soderberg, Lynn Denekamp, Sarah Nikiforow, Karen Sautter, Ronald C. Desrosiers, Louis Alexander

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

A recombinant simian immunodeficiency virus (SIV) derived from strain 239 (SIVmac239) with reverse transcriptase (RT) sequences from human immunodeficiency virus type 1 (HIV-1) strain HXB2 was severely impaired for replication. Detectable p27Gag levels were not observed until day 65 and peak p27Gag levels were not reached until day 75 after transfection of CEMx174 cells with the recombinant DNA. Sequences from the latter time point did not contain amino acid substitutions in HIV-1 RT; however, a single nucleotide substitution (thymine to cytosine) was found at position eight of the SIV primer binding site. We engineered an RT/SHIV genome with the thymine-to-cytosine substitution, called RT/SHIV/TC, and observed dramatically faster replication kinetics than were observed with the parental RT/SHIV from which this variant was derived. RT/SHIV/TC provides an improved system for study of the impact of drug resistance mutations in HIV-1 RT in a relevant animal model.

Original languageEnglish (US)
Pages (from-to)5803-5806
Number of pages4
JournalJournal of virology
Volume76
Issue number11
DOIs
StatePublished - May 27 2002

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'A nucleotide substitution in the tRNA<sup>Lys</sup> primer binding site dramatically increases replication of recombinant simian immunodeficiency virus containing a human immunodeficiency virus type 1 reverse transcriptase'. Together they form a unique fingerprint.

  • Cite this