Mutations generated in human immunodeficiency virus type 1 long terminal repeat during vertical transmission correlate with viral gene expression

Roshni Mehta, Vasudha Sundaravaradan, Nafees - Ahmad

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

We determined the effect of mutations generated in HIV-1 LTR on viral gene expression in six mother-infant pairs following vertical transmission. We show that the functional domains critical for LTR function, the promoter (TATAA), enhancers (three SpI and two NFκB sites), the modulatory region (two AP-I sites, two NFAT, one NF-IL6 site, one Ets-1, and one USF-1) and the TAR region were generally conserved among mother-infant pairs, although we observed several patient and pair specific mutations in these important domains. We then determined the promoter activity of our mother-infant LTR sequences by measuring CAT gene expression, which was driven by these LTRs and found that most of these HIV-1 LTRs derived from 6 mother-infant pairs were functional. However, mutations in the important transcription factor binding sites, including TATAA, SpI, NFκB, AP-I, NFAT, NF-IL6, Ets-1, USF-1 and TAR resulted in reduced LTR driven CAT gene expression. Taken together, conservation of functional domains in the LTR during vertical transmission supports the notion that a functional LTR is critical in viral replication and pathogenesis and mutations generated during the course of infection correlated with HIV-1 gene expression.

Original languageEnglish (US)
Pages (from-to)170-181
Number of pages12
JournalVirology
Volume375
Issue number1
DOIs
Publication statusPublished - May 25 2008

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Keywords

  • HIV-1 gene expression
  • HIV-1 LTR
  • HIV-1 vertical transmission
  • Mutations

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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