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Journal of Virology, January 2007, p. 677-688, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.00870-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Nuclear Import of the Preintegration Complex Is Blocked upon Infection by Human Immunodeficiency Virus Type 1 in Mouse Cells{triangledown}

Naomi Tsurutani,1,{dagger} Jiro Yasuda,1,2 Naoki Yamamoto,3 Byung-Il Choi,1 Motohiko Kadoki,1 and Yoichiro Iwakura1*

Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,1 Fifth Biology Section for Microbiology, Department of First Forensic Science, National Research Institute of Police Science, Kashiwa 277-0882,2 Department of Molecular Virology, School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan3

Received 28 April 2006/ Accepted 17 October 2006

Mouse cells do not support human immunodeficiency virus type 1 (HIV-1) replication because of host range barriers at steps including virus entry, transcription, RNA splicing, polyprotein processing, assembly, and release. The exact mechanisms for the suppression, however, are not completely understood. To elucidate further the barriers against HIV-1 replication in mouse cells, we analyzed the replication of the virus in lymphocytes from human CD4/CXCR4 transgenic mice. Although primary splenocytes and thymocytes allowed the entry and reverse transcription of HIV-1, the integration efficiency of the viral DNA was greatly reduced in these cells relative to human peripheral blood mononuclear cells, suggesting an additional block(s) before or at the point of host chromosome integration of the viral DNA. Preintegration processes were further analyzed using HIV-1 pseudotyped viruses. The reverse transcription step of HIV-1 pseudotyped with the envelope of murine leukemia virus or vesicular stomatitis virus glycoprotein was efficiently supported in both human and mouse cells, but nuclear import of the preintegration complex (PIC) of HIV-1 was blocked in mouse cells. We found that green fluorescent protein (GFP)-labeled HIV-1 integrase, which is known to be important in the nuclear localization of the PIC, could not be imported into the nucleus of mouse cells, in contrast to human cells. On the other hand, GFP-Vpr localized exclusively to the nuclei of both mouse and human cells. These observations suggest that, due to the dysfunction of integrase, the nuclear localization of PIC is suppressed in mouse cells.

* Corresponding author. Mailing address: Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81 3 5449 5536. Fax: 81 3 5449 5430. E-mail: iwakura{at}ims.u-tokyo.ac.jp.

{triangledown} Published ahead of print on 1 November 2006.

{dagger} Present address: Laboratory of Viral Infection II, Kitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, Japan.

Journal of Virology, January 2007, p. 677-688, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.00870-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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