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Mechanisms associated with the generation of biologically active human immunodeficiency virus type 1 particles from defective proviruses.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1991 Mar 15; Vol. 88 (6), pp. 2278-82. - Publication Year :
- 1991
-
Abstract
- The human immunodeficiency virus (HIV) is the etiological agent of acquired immunodeficiency syndrome (AIDS). HIV exhibits extensive genetic diversity and it is apparent that an infected individual contains different populations of distinct viral strains, a large proportion of which has been found surprisingly to be defective for replication. A similar phenomenon has also been observed with some cell lines that are known to produce infectious viral particles but harbor defective proviral genomes. Here, we investigated the molecular basis of this phenomenon by cloning proviral genomes of HIV from a cell line that was capable of producing high titers of biologically active HIV particles that readily induced syncytia with CD4+ cell lines and peripheral blood lymphocytes. This cell line was found to contain five proviral genomes, all of which, when tested individually, failed to produce replication-competent viruses upon transfection into human cells. However, when a specific combination of two proviral genomes was used in such transfection studies, it was possible to obtain biologically active, replication-competent viral particles that infected and replicated in CD4+ cell lines and induced syncytia characteristic of HIV. Such a result may be due to homologous recombination between proviral DNAs occurring in cells after transfection and/or complementation of replication-defective proviral DNAs. The diploid nature of the viral RNA genome present in the viral particle may enable the persistence of defective HIV genomes.
- Subjects :
- Cell Line
Cloning, Molecular
DNA, Viral genetics
DNA, Viral isolation & purification
Defective Viruses genetics
Gene Library
HIV-1 genetics
Humans
Proviruses genetics
Restriction Mapping
Rhabdomyosarcoma
Transfection
Defective Viruses physiology
Genes, Viral
HIV Long Terminal Repeat
HIV-1 physiology
Proviruses physiology
Virus Replication
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 88
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 2006168
- Full Text :
- https://doi.org/10.1073/pnas.88.6.2278