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Journal of Virology, October 2007, p. 10687-10698, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00653-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Transduction of Human Immunodeficiency Virus Type 1 Vectors Lacking Encapsidation and Dimerization Signals{triangledown}

Nihay Laham-Karam and Eran Bacharach*

Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv 69978, Israel

Received 27 March 2007/ Accepted 13 July 2007

The encapsidation signal ({Psi}) and the nested dimerization initiation site are important for efficient packaging of human immunodeficiency virus type 1 (HIV-1) genomic RNA dimers. Consequently, these signals are included in all HIV-1 vectors. Here, we provide evidence demonstrating that these elements in such vectors are not absolutely required for vector transduction. In single-cycle infection assays, vectors with {Psi} deleted ({Delta}{Psi}) were transduced with only a two- to fivefold reduction compared to the wild type. The transduction of {Delta}{Psi} showed typical products of reverse transcription and vector integration; however, in vitro and in vivo dimerization assays demonstrated the lack of normal dimerization of the {Delta}{Psi} vector. The reduction in transduction reflected a similar reduction in packaging. Nevertheless, a relatively high specificity of packaging was retained, as the {Delta}{Psi} vector was encapsidated at a level 4 orders of magnitude higher than that for overexpressed, nonretroviral cellular mRNA and 15 orders of magnitude higher than that for a murine leukemia virus (MLV)-based vector, all containing the same reporter gene, suggesting a {Psi}-independent mechanism of packaging. The fact that HIV-1 and MLV vectors were encapsidated with a much higher level of efficiency than the cellular RNA suggests that the genomic RNAs of different retroviruses share common features and/or pathways that target them to encapsidation. Overall, these results formally demonstrate that packaging and dimerization signals are not required for the early stages of infection and can be deleted without risking a total loss of vector transduction. Deletion of these signals should enhance the safety of these vectors.

* Corresponding author. Mailing address: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Phone: 972-3-640-7692. Fax: 972-3-642-2046. E-mail: eranbac{at}post.tau.ac.il

{triangledown} Published ahead of print on 25 July 2007.

Journal of Virology, October 2007, p. 10687-10698, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00653-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Vetter, M. L., D'Aquila, R. T. (2009). Cytoplasmic APOBEC3G Restricts Incoming Vif-Positive Human Immunodeficiency Virus Type 1 and Increases Two-Long Terminal Repeat Circle Formation in Activated T-Helper-Subtype Cells. J. Virol. 83: 8646-8654 [Abstract] [Full Text]  


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