Nef expressed from human immunodeficiency virus type 1 extrachromosomal DNA downregulates CD4 on primary CD4+ T lymphocytes: implications for integrase inhibitors.
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.
Duke Scholars
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- nef Gene Products, Human Immunodeficiency Virus
- Virus Replication
- Virus Integration
- Virology
- Leukocytes, Mononuclear
- Humans
- HIV-1
- HIV Integrase Inhibitors
- HIV Integrase
- Gene Products, nef
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- nef Gene Products, Human Immunodeficiency Virus
- Virus Replication
- Virus Integration
- Virology
- Leukocytes, Mononuclear
- Humans
- HIV-1
- HIV Integrase Inhibitors
- HIV Integrase
- Gene Products, nef