Moesin regulates stable microtubule formation and limits retroviral infection in cultured cells

Mojgan H. Naghavi, Susana Valente, Theodora Hatziioannou, Kenia De Los Santos, Ying Wen, Christina Mott, Gregg G. Gundersen, Stephen P. Goff*

*Corresponding author for this work

Research output: Contribution to journalArticle

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)41-52
Number of pages12
JournalEMBO Journal
Volume26
Issue number1
DOIs
StatePublished - Jan 10 2007

Keywords

  • HIV-1
  • Moesin
  • Retroviruses
  • Stable microtubules
  • Viral block

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Naghavi, M. H., Valente, S., Hatziioannou, T., De Los Santos, K., Wen, Y., Mott, C., Gundersen, G. G., & Goff, S. P. (2007). Moesin regulates stable microtubule formation and limits retroviral infection in cultured cells. EMBO Journal, 26(1), 41-52. https://doi.org/10.1038/sj.emboj.7601475