Location: Animal Disease ResearchTitle: Ovine herpesvirus 2 glycoproteins B, H, and L are sufficient for, and viral glycoprotein Ov8 can enhance, cell-cell membrane fusion Author
|Alhajri, S - Washington State University|
|Nicola, Anthony - Washington State University|
|Aguilar, Hector - Washington State University|
Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/26/2016
Publication Date: 1/4/2017
Citation: Alhajri, S.M., Cunha, C.W., Nicola, A.V., Aguilar, H.C., Li, H., Taus, N.S. 2017. Ovine herpesvirus 2 glycoproteins B, H, and L are sufficient for, and viral glycoprotein Ov8 can enhance, cell-cell membrane fusion. Journal of Virology. doi: 10.1128/JVI.02454-16.
Interpretive Summary: Herpesviruses enter cells by attaching to the cellular surface and fusing with cellular membranes. Virus-cell membrane fusion is an important step for a successful viral infection. Elucidating viral proteins that are responsible for membrane fusion is an important step toward understanding viral entry. Entry of ovine herpesvirus 2 (OvHV-2), the causative agent of sheep associated malignant catarrhal fever, which is one of the leading causes of deaths in bison and other ruminants, has not been well-studied due to the lack of cell culture to propagate the virus. Using a virus-free fusion assay three core herpesvirus proteins were shown to be necessary and sufficient to mediate membrane fusion. A fourth OvHV-2 unique protein was shown to enhance fusion. The identification of OvHV-2 proteins that mediate membrane fusion will advance investigation of cellular factors necessary for mediating virus-cell membrane fusion and may help identify viral and/or cellular factors involved in directing OvHV-2 to specific cell types. Advances in these areas of study could lead to development of means, such as vaccines, to prevent disease in susceptible animals.
Technical Abstract: Ovine herpesvirus 2 (OvHV-2) is a gammaherpesvirus in the genus Macavirus that is carried asymptomatically by sheep. Infection of poorly adapted animals with OvHV-2 results in sheep associated malignant catarrhal fever, a fatal disease characterized by lymphoproliferation and vasculitis. There is no treatment or vaccine for this virus and no cell culture to propagate it. The lack of cell culture has hindered studies on OvHV-2 biology including its entry mechanism. As an alternative method to study OvHV-2 glycoproteins responsible for membrane fusion as a part of the entry mechanism, we developed a virus free cell-to-cell membrane fusion assay. In this study we identified the minimum required OvHV-2 glycoproteins to induce membrane fusion. OvHV-2 glycoproteins gB, gH and gL together were able to induce membrane fusion but not when expressed individually. Cell-cell membrane fusion was detected by both fluorescence microscopy and reporter gene expression. Open reading frame Ov8, unique to OvHV-2, was found to encode a monomeric transmembrane glycoprotein that can significantly enhance membrane fusion. Thus, the OvHV-2 glycoproteins gB, gH and gL are required and sufficient to induce membrane fusion. Glycoprotein Ov8 plays an enhancing role by an unknown mechanism, possibly by receptor binding.