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The dimer initiation sequence stem-loop of human immunodeficiency virus type 1 is dispensable for viral replication in peripheral blood mononuclear cells

Hill, M. K., Shehu-Xhilaga, M., Campbell, S. M., Poumbourios, P., Crowe, S. M. and Mak, J. 2003, The dimer initiation sequence stem-loop of human immunodeficiency virus type 1 is dispensable for viral replication in peripheral blood mononuclear cells, Journal of virology, vol. 77, no. 15, pp. 8329-8335, doi: 10.1128/JVI.77.15.8329-8335.2003.

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Title The dimer initiation sequence stem-loop of human immunodeficiency virus type 1 is dispensable for viral replication in peripheral blood mononuclear cells
Author(s) Hill, M. K.
Shehu-Xhilaga, M.
Campbell, S. M.
Poumbourios, P.
Crowe, S. M.
Mak, J.ORCID iD for Mak, J. orcid.org/0000-0002-5229-5707
Journal name Journal of virology
Volume number 77
Issue number 15
Start page 8329
End page 8335
Total pages 7
Publisher American Society for Microbiology
Place of publication Washington, D. C.
Publication date 2003-08
ISSN 0022-538X
1098-5514
Keyword(s) dimer
gag protein
genomic RNA
nucleotide
pol protein
pro protein
protein precursor
unclassified drug
virus protein
Summary Human immunodeficiency virus type 1 (HIV-1) contains two copies of genomic RNA that are noncovalently linked via a palindrome sequence within the dimer initiation site (DIS) stem-loop. In contrast to the current paradigm that the DIS stem or stem-loop is critical for HIV-1 infectivity, which arose from studies using T-cell lines, we demonstrate here that HIV-1 mutants with deletions in the DIS stem-loop are replication competent in peripheral blood mononuclear cells (PBMCs). The DIS mutants contained either the wild-type (5′GCGCGC3′) or an arbitrary (5′ACGCGT3′) palindrome sequence in place of the 39-nucleotide DIS stem-loop (NLCGCGCG and NLACGCGT). These DIS mutants were replication defective in SupT1 cells, concurring with the current model in which DIS mutants are replication defective in T-cell lines. All of the HIV-1 DIS mutants were replication competent in PBMCs over a 40-day infection period and had retained their respective DIS mutations at 40 days postinfection. Although the stability of the virion RNA dimer was not affected by our DIS mutations, the RNA dimers exhibited a diffuse migration profile when compared to the wild type. No defect in protein processing of the Gag and GagProPol precursor proteins was found in the DIS mutants. Our data provide direct evidence that the DIS stem-loop is dispensable for viral replication in PBMCs and that the requirement of the DIS stem-loop in HIV-1 replication is cell type dependent.
Language eng
DOI 10.1128/JVI.77.15.8329-8335.2003
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 ©2003, American Society for Microbiology
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047536

Document type: Journal Article
Collections: School of Medicine
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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.