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Moesin regulates stable microtubule formation and limits retroviral infection in cultured cells
Author(s) -
Naghavi Mojgan H,
Valente Susana,
Hatziioannou Theodora,
de los Santos Kenia,
Wen Ying,
Mott Christina,
Gundersen Gregg G,
Goff Stephen P
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601475
Subject(s) - biology , microtubule , microbiology and biotechnology , virology , moesin , cytoskeleton , genetics , cell , ezrin
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.