Mutations generated in human immunodeficiency virus type 1 long terminal repeat during vertical transmission correlate with viral gene expression.
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 NFkappaB 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, NFkappaB, 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.
Mehta
Roshni
R
Department of Immunobiology, College of Medicine, The University of Arizona, 1501 N. Campbell Avenue, Tucson, Arizona 85724, USA.
Sundaravaradan
Vasudha
V
Ahmad
Nafees
N
D000328:Adult; D019677:Artificial Gene Fusion; D001483:Base Sequence; D001665:Binding Sites; D002675:Child, Preschool; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008969:Molecular Sequence Data; D009035:Mothers; D009154:Mutation; D011401:Promoter Regions, Genetic; D020079:Terminal Repeat Sequences / Q000235:genetics*
D015500:Chloramphenicol O-Acetyltransferase