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Nef expressed from human immunodeficiency virus type 1 extrachromosomal DNA downregulates CD4 on primary CD4+ T lymphocytes: implications for integrase inhibitors

Authors :
Andrea Cara
Mary E. Klotman
Laura Gillim-Ross
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.

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