Back to Search
Start Over
Nef expressed from human immunodeficiency virus type 1 extrachromosomal DNA downregulates CD4 on primary CD4+ T lymphocytes: implications for integrase inhibitors
- Source :
- Journal of General Virology. 86:765-771
- Publication Year :
- 2005
- Publisher :
- Microbiology Society, 2005.
-
Abstract
- Recently developed integrase inhibitors targeting the HIV-1 integrase (IN) protein block integration of HIV DNA in the target cell, preventing subsequent virus replication. In the absence of integration, viral DNA is shunted towards the formation of extrachromosomal DNA (E-DNA). Although HIV-1 E-DNA does not support productive replication, it is transcriptionally active and produces viral proteins. However, the significance of E-DNA in virus replication and pathogenesis is poorly understood. In this study, the functional activity of the HIV-1 Nef protein expressed in the absence of viral integration was analysed. Using both a recombinant HIV-1 IN defective virus and a diketo acid IN inhibitor, evidence was provided showing that Nef expressed from E-DNA downregulates CD4 surface expression on primary CD4+ T lymphocytes. These results suggest that proteins expressed in the absence of integration may have potential clinical consequences, an issue that should be further explored with the introduction of IN inhibitors.
- Subjects :
- CD4-Positive T-Lymphocytes
Virus Integration
viruses
Down-Regulation
Integrase inhibitor
HIV Integrase
Biology
Virus Replication
Gene Products, nef
Defective virus
Virus
law.invention
chemistry.chemical_compound
law
Virology
Extrachromosomal DNA
Humans
HIV Integrase Inhibitors
nef Gene Products, Human Immunodeficiency Virus
Cells, Cultured
Integrase
Viral replication
chemistry
CD4 Antigens
DNA, Viral
HIV-1
Leukocytes, Mononuclear
Recombinant DNA
biology.protein
DNA
Subjects
Details
- ISSN :
- 14652099 and 00221317
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- Journal of General Virology
- Accession number :
- edsair.doi.dedup.....512f7ba64dfc2699263679c5252806d4
- Full Text :
- https://doi.org/10.1099/vir.0.80570-0