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Journal of Virology, August 2003, p. 8329-8335, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8329-8335.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Dimer Initiation Sequence Stem-Loop of Human Immunodeficiency Virus Type 1 Is Dispensable for Viral Replication in Peripheral Blood Mononuclear Cells

M. K. Hill,1 M. Shehu-Xhilaga,1,2 S. M. Campbell,1,3 P. Poumbourios,4 S. M. Crowe,1,2,5 and J. Mak1,6*

AIDS Pathogenesis Research Unit, The Macfarlane Burnet Institute for Medical Research and Public Health,1 Department of Medicine, Monash University,2 Department of Microbiology and Immunology, University of Melbourne,3 St. Vincent's Institute of Medical Research,4 National Centre for HIV Virology Research, Melbourne,5 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia6

Received 6 May 2002/ Accepted 14 May 2003

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.

* Corresponding author. Mailing address: The Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne, Victoria, Australia 3001. Phone: 61 3 9282 2217. Fax: 61 3 9482 2142. E-mail: mak{at}burnet.edu.au.

Journal of Virology, August 2003, p. 8329-8335, Vol. 77, No. 15
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.15.8329-8335.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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