The Human Metapneumovirus Small Hydrophobic Protein has Properties Consistent with Those of a Viroporin and Can Modulate Viral Fusogenic Activity

Authors

Cyril Masante, University of Kentucky
Farah El Najjar, University of KentuckyFollow
Andres Chang, University of Kentucky
Angela Jones, University of Kentucky
Carole L. Moncman, University of KentuckyFollow
Rebecca Ellis Dutch, University of KentuckyFollow

Abstract

Human metapneumovirus (HMPV) encodes three glycoproteins: the glycoprotein, which plays a role in glycosaminoglycan binding, the fusion (F) protein, which is necessary and sufficient for both viral binding to the target cell and fusion between the cellular plasma membrane and the viral membrane, and the small hydrophobic (SH) protein, whose function is unclear. The SH protein of the closely related respiratory syncytial virus has been suggested to function as a viroporin, as it forms oligomeric structures consistent with a pore and alters membrane permeability. Our analysis indicates that both the full-length HMPV SH protein and the isolated SH protein transmembrane domain can associate into higher-order oligomers. In addition, HMPV SH expression resulted in increases in permeability to hygromycin B and alteration of subcellular localization of a fluorescent dye, indicating that SH affects membrane permeability. These results suggest that the HMPV SH protein has several characteristics consistent with a putative viroporin. Interestingly, we also report that expression of the HMPV SH protein can significantly decrease HMPV F protein-promoted membrane fusion activity, with the SH extracellular domain and transmembrane domain playing a key role in this inhibition. These results suggest that the HMPV SH protein could regulate both membrane permeability and fusion protein function during viral infection.

IMPORTANCE: Human metapneumovirus (HMPV), first identified in 2001, is a causative agent of severe respiratory tract disease worldwide. The small hydrophobic (SH) protein is one of three glycoproteins encoded by all strains of HMPV, but the function of the HMPV SH protein is unknown. We have determined that the HMPV SH protein can alter the permeability of cellular membranes, suggesting that HMPV SH is a member of a class of proteins termed viroporins, which modulate membrane permeability to facilitate critical steps in a viral life cycle. We also demonstrated that HMPV SH can inhibit the membrane fusion function of the HMPV fusion protein. This work suggests that the HMPV SH protein has several functions, though the steps in the HMPV life cycle impacted by these functions remain to be clarified.

Document Type

Article

Publication Date

6-2014

Notes/Citation Information

Published in Journal of Virology, v. 88, no. 11, p. 6423-6433.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The copyright holders have granted the permission for posting the article here.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1128/JVI.02848-13

Funding Information

This work was supported by NIH grants R01AI051517 and 2P20 RR020171 from the National Center for Research Resources to R.E.D. and an AHA predoctoral fellowship to A.C.

Repository Citation

Masante, Cyril; Najjar, Farah El; Chang, Andres; Jones, Angela; Moncman, Carole L.; and Dutch, Rebecca Ellis, "The Human Metapneumovirus Small Hydrophobic Protein has Properties Consistent with Those of a Viroporin and Can Modulate Viral Fusogenic Activity" (2014). Molecular and Cellular Biochemistry Faculty Publications. 66.
https://uknowledge.uky.edu/biochem_facpub/66