Herpes B virus utilizes human nectin-1 but not HVEM or PILRα for cell-cell fusion and virus entry

Qing Fan, Melanie Amen, Mallory Harden, Alberto Severini, Anthony Griffiths, Richard Longnecker

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    19 Scopus citations

    Abstract

    To investigate the requirements of herpesvirus entry and fusion, the four homologous glycoproteins necessary for herpes simplex virus (HSV) fusion were cloned from herpes B virus (BV) (or macacine herpesvirus 1, previously known as cercopithecine herpesvirus 1) and cercopithecine herpesvirus 2 (CeHV-2), both related simian simplexviruses belonging to the alphaherpesvirus subfamily. Western blots and cell-based enzyme-linked immunosorbent assay (ELISA) showed that glycoproteins gB, gD, and gH/gL were expressed in whole-cell lysates and on the cell surface. Cell-cell fusion assays indicated that nectin-1, an HSV-1 gD receptor, mediated fusion of cells expressing glycoproteins from both BV and CeHV-2. However, herpesvirus entry mediator (HVEM), another HSV-1 gD receptor, did not facilitate BV- and CeHV-2-induced cell-cell fusion. Paired immunoglobulin-like type 2 receptor alpha (PILRα), an HSV-1 gB fusion receptor, did not mediate fusion of cells expressing glycoproteins from either simian virus. Productive infection with BV was possible only with nectin-1-expressing cells, indicating that nectin-1 mediated entry while HVEM and PILRα did not function as entry receptors. These results indicate that these alphaherpesviruses have differing preferences for entry receptors. The usage of the HSV-1 gD receptor nectin-1 may explain interspecies transfer of the viruses, and altered receptor usage may result in altered virulence, tropism, or pathogenesis in the new host. A heterotypic cell fusion assay resulting in productive fusion may provide insight into interactions that occur to trigger fusion. These findings may be of therapeutic significance for control of deadly BV infections.

    Original languageEnglish (US)
    Pages (from-to)4468-4476
    Number of pages9
    JournalJournal of Virology
    Volume86
    Issue number8
    DOIs
    Publication statusPublished - Apr 1 2012

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    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

    Cite this

    Fan, Q., Amen, M., Harden, M., Severini, A., Griffiths, A., & Longnecker, R. (2012). Herpes B virus utilizes human nectin-1 but not HVEM or PILRα for cell-cell fusion and virus entry. Journal of Virology, 86(8), 4468-4476. https://doi.org/10.1128/JVI.00041-12