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X4 and R5 HIV-1 have distinct post-entry requirements for uracil DNA glycosylase during infection of primary cells

Jones, Kate L., Roche, Michael, Gantier, Michael P., Begum, Nasim A., Honjo, Tasuku, Caradonna, Salvatore, Williams, Bryan R. G. and Mak, Johnson 2010, X4 and R5 HIV-1 have distinct post-entry requirements for uracil DNA glycosylase during infection of primary cells, Journal of biological chemistry, vol. 285, no. 24, pp. 18603-18614, doi: 10.1074/jbc.M109.090126.

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Title X4 and R5 HIV-1 have distinct post-entry requirements for uracil DNA glycosylase during infection of primary cells
Author(s) Jones, Kate L.
Roche, Michael
Gantier, Michael P.
Begum, Nasim A.
Honjo, Tasuku
Caradonna, Salvatore
Williams, Bryan R. G.
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Journal name Journal of biological chemistry
Volume number 285
Issue number 24
Start page 18603
End page 18614
Total pages 12
Publisher American Society for Biochemistry and Molecular Biology
Place of publication Bethesda, Md.
Publication date 2010-06-11
ISSN 0021-9258
1083-351X
Keyword(s) HIV
reverse transcription
RNA viruses
siRNA
viral replication
virus entry
DNA repairing enzyme
HIV uncoating
viral tropism
Summary It has been assumed that R5 and X4 HIV utilize similar strategies to support viral cDNA synthesis post viral entry. In this study, we provide evidence to show that R5 and X4 HIV have distinct requirements for host cell uracil DNA glycosylase (UNG2) during the early stage of infection. UNG2 has been previously implicated in HIV infection, but its precise role remains controversial. In this study we show that, although UNG2 is highly expressed in different cell lines, UNG2 levels are low in the natural host cells of HIV. Short interfering RNA knockdown of endogenous UNG2 in primary cells showed that UNG2 is required for R5 but not X4 HIV infection and that this requirement is bypassed when HIV enters the target cell via vesicular stomatitis virus envelope-glycoprotein-mediated endocytosis. We also show that short interfering RNA knockdown of UNG2 in virus-producing primary cells leads to defective R5 HIV virions that are unable to complete viral cDNA synthesis. Quantitative PCR analysis revealed that endogenous UNG2 levels are transiently up-regulated post HIV infection, and this increase in UNG2 mRNA is ∼10–20 times higher in R5 versus X4 HIV-infected cells. Our data show that both virion-associated UNG2 and HIV infection-induced UNG2 expression are critical for reverse transcription during R5 but not X4 HIV infection. More importantly, we have made the novel observation that R5 and X4 HIV have distinct host cell factor requirements and differential capacities to induce gene expression during the early stages of infection. These differences may result from activation of distinct signaling cascades and/or infection of divergent T-lymphocyte subpopulations.
Language eng
DOI 10.1074/jbc.M109.090126
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2010, American Society for Biochemistry and Molecular Biology
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047507

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.