Article
- The EMBO Journal (2007) 26, 41 - 52
- doi:10.1038/sj.emboj.7601475
Published online: 14 December 2006
Subject Categories:
Moesin regulates stable microtubule formation and limits retroviral infection in cultured cells
Mojgan H Naghavi1,a, Susana Valente1, Theodora Hatziioannou2, Kenia de los Santos1, Ying Wen3, Christina Mott1, Gregg G Gundersen3 and Stephen P Goff1
- Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY, USA
- Aaron Diamond AIDS Research Center, New York, NY, USA
- Department of Anatomy and Cell Biology, Columbia University, New York, NY, USA
Correspondence to:
Stephen P Goff, Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, HHSC 1310, 701 West 168th Street, New York, NY 10032, USA. Tel.: +1 212 305 7956; Fax: +1 212 305 5106; E-mail: goff@cancercenter.columbia.edu
aPresent address: Center for Research in Infectious Diseases, Conway Institute of Molecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
Received 11 July 2006; Accepted 6 November 2006
Abstract
In a functional screen of mammalian complementary DNA libraries, we identified moesin as a novel gene whose overexpression blocks infection by murine leukemia viruses and human immunodeficiency virus type 1 in human and rodent lines, before the initiation of reverse transcription. Knockdown of moesin by RNA interference resulted in enhanced infection, suggesting that even the endogenous basal levels of moesin in rat fibroblasts are sufficient to limit virus infection. Moesin acts as a crosslinker between plasma membrane and actin filaments, as well as a signal transducer in responses involving cytoskeletal remodeling. Moesin overexpression was found to downregulate the formation of stable microtubules, whereas knockdown of moesin increased stable microtubule formation. A virus-resistant mutant cell line also displayed decreased stable microtubule levels, and virus-sensitive revertants recovered from the mutant line showed restoration of the stable microtubules, suggesting that these cytoskeletal networks play an important role in early post-entry events in the retroviral lifecycle. Together, these results suggest that moesin negatively regulates stable microtubule networks and is a natural determinant of cellular sensitivity to retroviral infection.
Keywords:
- HIV-1,
- moesin,
- retroviruses,
- stable microtubules,
- viral block
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