Genotypic and Phenotypic Heterogeneity in the U3R Region of HIV Type 1 Subtype C
| Autor: | William E. Ackerman, Jesse J. Kwiek, Igor O. Voronkin, Megan Mefford, Samuel K. Handelman, Jose A. Bazan, Victor Mwapasa, Daniel Janies, Jessica M. Mates, Surender B. Kumar |
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| Rok vydání: | 2014 |
| Předmět: |
Malawi
Genotype Transcription Genetic 5' Flanking Region Immunology 5' flanking region HIV Infections Biology Polymorphism Single Nucleotide Cell Line Jurkat Cells Young Adult Pregnancy Virology HIV Seropositivity Genetic variation Humans nef Gene Products Human Immunodeficiency Virus Pregnancy Complications Infectious Promoter Regions Genetic HIV Long Terminal Repeat Genetics Binding Sites Base Sequence Genetic heterogeneity NF-kappa B Genetic Variation Infant virus diseases Promoter Sequence Analysis DNA Viral Load Infectious Disease Transmission Vertical Long terminal repeat CD4 Lymphocyte Count HEK293 Cells Infectious Diseases HIV-1 Female Sequence Alignment Viral load Transcription Factors |
| Zdroj: | AIDS Research and Human Retroviruses. 30:102-112 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2013.0026 |
| Popis: | Approximately 20% of all HIV-1 mother-to-child transmission (MTCT) occurs in utero (IU). In a chronic HIV infection, HIV-1 exists as a complex swarm of genetic variants, and following IU MTCT, viral genomic diversity is restricted through a mechanism that remains to be described. The 5' U3R region of the HIV-1 long terminal repeat (LTR) contains multiple transcription factor (TF) binding sites and regulates viral transcription. In this study, we tested the hypothesis that sequence polymorphisms in the U3R region of LTR are associated with IU MTCT. To this end, we used single template amplification to isolate 517 U3R sequences from maternal, placental, and infant plasma derived from 17 HIV-infected Malawian women: eight whose infants remained HIV uninfected (NT) and nine whose infants became HIV infected IU. U3R sequences show pairwise diversities ranging from 0.2% to 2.3%. U3R sequences from one participant contained two, three, or four putative NF-κB binding sites. Phylogenetic reconstructions indicated that U3R sequences from eight of nine IU participants were consistent with placental compartmentalization of HIV-1 while only one of eight NT cases was consistent with such compartmentalization. Specific TF sequence polymorphisms were not significantly associated with IU MTCT. To determine if replication efficiency of the U3R sequences was associated with IU MTCT, we cloned 90 U3R sequences and assayed promoter activity in multiple cell lines. Although we observed significant, yet highly variable promoter activity and TAT induction of promoter activity in the cell lines tested, there was no association between measured promoter activity and MTCT status. Thus, we were unable to detect a promoter genotype or phenotype associated with IU MTCT. |
| Databáze: | OpenAIRE |
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