Human metapneumovirus Induces Reorganization of the Actin Cytoskeleton for Direct Cell-to-Cell Spread

PLoS Pathogens

Jing Chen¹  Carole L. Moncman¹  Nicolás Cifuentes-Muñoz¹  Rebecca Ellis Dutch¹  Farah El Najjar¹  Haining Zhu¹  Ursula J. Buchholz² 

[1] Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America;Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America

关键词: Actins;    Membrane proteins;    Cell membranes;    Respiratory infections;    Viral structure;    Antibodies;    Actin polymerization;    Cell staining;   

DOI  :  10.1371/journal.ppat.1005922

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. In contrast, inhibition of actin polymerization or alterations to Rho GTPase signaling pathways significantly decreased cell-to-cell spread. Furthermore, viral proteins and viral RNA were detected in intercellular extensions, suggesting direct transfer of viral genetic material to new target cells. While roles for paramyxovirus matrix and fusion proteins in membrane deformation have been previously demonstrated, we show that the HMPV phosphoprotein extensively co-localized with actin and induced formation of cellular extensions when transiently expressed, supporting a new model in which a paramyxovirus phosphoprotein is a key player in assembly and spread. Our results reveal a novel mechanism for HMPV direct cell-to-cell spread and provide insights into dissemination of respiratory viruses.

【 授权许可】

CC BY