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A novel HIV-1 isolate containing alterations affecting the NF-kappa B element.
G Englund1, M D Hoggan, T S Theodore
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Virology
|March 1, 1991
Summary
Distinct HIV-1 clones showed varied replication due to changes in the viral LTR enhancer. These alterations, involving NF-kappa B motifs, impacted promoter activity and viral capacity.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) exhibits genetic diversity.
- Understanding the molecular basis of HIV-1 replication and pathogenesis is crucial for therapeutic development.
Purpose of the Study:
- To investigate the molecular determinants of distinct replicative and cytopathic properties among HIV-1 clones.
- To elucidate the role of the viral Long Terminal Repeat (LTR) enhancer region in HIV-1 phenotypic variation.
Main Methods:
- Propagation of HIV-1 molecular clones in human T cell lines.
- Nucleotide sequencing and Polymerase Chain Reaction (PCR) analysis to identify genetic alterations.
- Construction and analysis of LTR-driven CAT (chloramphenicol acetyltransferase) expression vectors.
Main Results:
- Three HIV-1 clones from a single isolate (AL1) displayed significant differences in replication and cytopathic effects.
- Phenotypic variations were largely attributed to modifications within the viral LTR, specifically involving duplications or deletions of the NF-kappa B motif.
- These LTR alterations were present in the original AL1 virus stock.
- Subcloning experiments confirmed a direct correlation between NF-kappa B enhancer activity and viral replicative/cytopathic capacity.
Conclusions:
- The NF-kappa B motif within the HIV-1 LTR enhancer is a critical determinant of viral replication and cytopathic potential.
- Genetic variations in enhancer elements can lead to distinct phenotypic properties within HIV-1 populations.
- These findings highlight the importance of enhancer region plasticity in HIV-1 evolution and pathogenesis.