Retrovirology

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Impaired nuclear import and viral incorporation of Vpr derived from a HIV long-term non-progressor

Leon Caly1, Nitin K Saksena2, Sabine C Piller3,4 and David A Jans1*

Author Affiliations

1 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia

2 Retroviral Genetics Division, Centre for Virus Research, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Darcy Road, Westmead, N.S.W 2145, Australia

3 HIV Protein Function and Interactions Group, Centre for Virus Research, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Darcy Road, Westmead, N.S.W 2145, Australia

4 University of Western Sydney, Penrith South DC, N.S.W 1797, Australia

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Retrovirology 2008, 5:67 doi:10.1186/1742-4690-5-67

Published: 18 July 2008

Abstract

We previously reported an epidemiologically linked HIV-1 infected patient cohort in which a long-term non-progressor (LTNP) infected two recipients who then exhibited normal disease progression. Expression of patient-derived vpr sequences from each of the three cohort members in mammalian cells tagged with GFP revealed a significant reduction in Vpr nuclear import and virion incorporation uniquely from the LTNP, whereas Vpr from the two progressing recipients displayed normal localisation and virion incorporation, implying a link between efficient Vpr nuclear import and HIV disease progression. Importantly, an F72L point mutation in the LTNP was identified for the first time as being uniquely responsible for decreased Vpr nuclear import.