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Journal of Virology, August 2007, p. 7985-7992, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00429-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Minimal Region Sufficient for Genome Dimerization in the Human Immunodeficiency Virus Type 1 Virion and Its Potential Roles in the Early Stages of Viral Replication{triangledown}

Jun-ichi Sakuragi,* Sayuri Sakuragi, and Tatsuo Shioda

Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Received 28 February 2007/ Accepted 11 May 2007

It has been suggested that the dimer initiation site/dimer linkage sequence (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome plays an important role at various stages of the viral life cycle. Recently we found that the duplication of the DIS/DLS region on viral RNA caused the production of partially monomeric RNAs in virions, indicating that this region indeed mediates RNA-RNA interaction. In this report, we followed up on this finding to identify the necessary and sufficient region for RNA dimerization in the virion of HIV-1. The region thus identified was 144 bases in length, extending from the junction of R/U5 and U5/L stem-loops to the end of SL4. The trans-acting responsive element, polyadenylation signal, primer binding site, upper stem-loop of U5/L, and SL2 were not needed for the function of this region. The insertion of this region into the ectopic location of the viral genome did not affect the level of virion production by transfection. However, the resultant virions contained monomerized genomes and showed drastic reductions in infectivity. A reduction was observed especially in the reverse transcription process. An attempt to generate a replication-competent virus with monomerized genome was performed by the long-term culture of mutant virus-infected cells. All recovered viruses were wild-type revertants, indicating a fatal defect of the mutation. These results suggest that genome dimerization or DIS/DLS itself also plays an important role in the early stages of virus infection.

* Corresponding author. Mailing address: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka 565-0871, Japan. Phone: 81-6-6879-834. Fax: 81-6-6879-8347. E-mail: sakuragi{at}biken.osaka-u.ac.jp

{triangledown} Published ahead of print on 15 May 2007.

Journal of Virology, August 2007, p. 7985-7992, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00429-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jones, K. L., Sonza, S., Mak, J. (2008). Primary T-lymphocytes rescue the replication of HIV-1 DIS RNA mutants in part by facilitating reverse transcription. Nucleic Acids Res 36: 1578-1588 [Abstract] [Full Text]  


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