Journal article
Cellular specificity of HIV-1 replication can be controlled by LTR sequences
Virology (New York, N.Y.), Vol.314(2), pp.680-695
2003
DOI: 10.1016/S0042-6822(03)00508-7
PMID: 14554095
Abstract
Two well-established determinants of retroviral tropism are envelope sequences that regulate entry and LTR sequences that can regulate viral expression in a cell-specific manner. Studies with human immunodeficiency virus-1 (HIV-1) have demonstrated that tropism of this virus maps primarily to variable envelope sequences. Studies have demonstrated that T cell and macrophage-specific transcription factor binding motifs exist in the upstream region of the LTR U3; however, the ability of the core enhancer/promoter proximal elements (two NF-κB and three Sp1 sites) to function well in macrophages and T cells have led many to conclude that HIV LTR sequences are not primary determinants of HIV tropism. To determine if cellular specificity could be imparted to HIV by the core enhancer elements, the enhancer/promoter proximal region of the HIV LTR was substituted with motifs that control gene expression in a myeloid-specific manner. The enhancer region from equine infectious anemia virus (EIAV) when substituted for the HIV enhancer/promoter proximal region was found to drive expression in a macrophage-specific manner and was responsive to HIV Tat. The addition of a 5′ methylation-dependent binding site (MDBP) and a promoter proximal Sp1 motif increased expression without altering cellular specificity. Spacing between the promoter proximal region and the TATA box was also found to influence LTR activity. Infectivity studies using chimeric LTRs within the context of a dual-tropic infectious molecular clone established that these LTRs directed HIV replication and production of infectious virions in macrophages but not primary T cells or T cell lines. This investigation demonstrates that cellular specificity can be imparted onto HIV-1 replication at the level of viral transcription and not entry.
Details
- Title: Subtitle
- Cellular specificity of HIV-1 replication can be controlled by LTR sequences
- Creators
- Edward Reed-Inderbitzin - Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, SD 57069, USAWendy Maury - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Virology (New York, N.Y.), Vol.314(2), pp.680-695
- DOI
- 10.1016/S0042-6822(03)00508-7
- PMID
- 14554095
- NLM abbreviation
- Virology
- ISSN
- 0042-6822
- eISSN
- 1096-0341
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2003
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083857802771
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