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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gillim-Ross, L; Cara, A; Klotman, ME

Published Date

  • March 2005

Published In

Volume / Issue

  • 86 / Pt 3

Start / End Page

  • 765 - 771

PubMed ID

  • 15722538

International Standard Serial Number (ISSN)

  • 0022-1317

Digital Object Identifier (DOI)

  • 10.1099/vir.0.80570-0


  • eng

Conference Location

  • England