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Journal of Virology, June 2008, p. 5860-5868, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00076-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The LEM Domain Proteins Emerin and LAP2{alpha} Are Dispensable for Human Immunodeficiency Virus Type 1 and Murine Leukemia Virus Infections{triangledown} ,{dagger}

Alok Mulky,1 Tatiana V. Cohen,2 Serguei V. Kozlov,2 Barbara Korbei,3 Roland Foisner,3 Colin L. Stewart,2* and Vineet N. KewalRamani1*

HIV Drug Resistance Program,1 Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702,2 Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria3

Received 11 January 2008/ Accepted 31 March 2008

The human nuclear envelope proteins emerin and lamina-associated polypeptide 2{alpha} (LAP2{alpha}) have been proposed to aid in the early replication steps of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). However, whether these factors are essential for HIV-1 or MLV infection has been questioned. Prior studies in which conflicting results were obtained were highly dependent on RNA interference-mediated gene silencing. To shed light on these contradictory results, we examined whether HIV-1 or MLV could infect primary cells from mice deficient for emerin, LAP2{alpha}, or both emerin and LAP2{alpha}. We observed HIV-1 and MLV infectivity in mouse embryonic fibroblasts (MEFs) from emerin knockout, LAP2{alpha} knockout, or emerin and LAP2{alpha} double knockout mice to be comparable in infectivity to wild-type littermate-derived MEFs, indicating that both emerin and LAP2{alpha} were dispensable for HIV-1 and MLV infection of dividing, primary mouse cells. Because emerin has been suggested to be important for infection of human macrophages by HIV-1, we also examined HIV-1 transduction of macrophages from wild-type mice or knockout mice, but again we did not observe a difference in susceptibility. These findings prompted us to reexamine the role of human emerin in supporting HIV-1 and MLV infection. Notably, both viruses efficiently infected human cells expressing high levels of dominant-negative emerin. We thus conclude that emerin and LAP2{alpha} are not required for the early replication of HIV-1 and MLV in mouse or human cells.


* Corresponding author. Mailing address for Vineet N. KewalRamani: HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702-1201. Phone: (301) 846-1249. Fax: (301) 846-6777. E-mail: vineet{at}ncifcrf.gov. Present address for Colin L. Stewart: Institute for Medical Biology, 03-03 Proteos, 61 Biopolis Drive, Singapore 113867, Singapore. E-mail: colin.stewart{at}imb.a-star.edu.sg

{triangledown} Published ahead of print on 9 April 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.


Journal of Virology, June 2008, p. 5860-5868, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.00076-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.







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