Structural rearrangement within an enveloped virus upon binding to the host cell

David G. Meckes, John W. Wills

    Research output: Contribution to journalArticlepeer-review

    33 Scopus citations

    Abstract

    We have made the surprising discovery that the interactions of herpes simplex virus with its initial cell attachment receptor induce a rapid and highly efficient structural change in the tegument, the region of the virion situated between the membrane and the capsid. It has been known for nearly a decade that viruses can trigger host signaling pathways when they bind to receptors on the cell surface; however, until now there has been no evidence that a signal can be sent in reverse - from the "outside in" - across a viral membrane. Evidence for this signaling event was found during studies of UL16, a tegument protein that is conserved among all the herpesviruses. Previous work has demonstrated that UL16 is bound to capsids isolated from the cytoplasm of infected cells, but this interaction is destabilized during subsequent egress steps, leading to release of the extracellular virion. Pretreatment with N-ethylmaleimide, a small, membrane-permeating compound that covalently modifies free cysteines, restabilizes the interaction, thereby permitting the capsid-UL16 complex to be isolated following disruption of virions with NP-40. In the experiments described here, we found that the natural signal for release of UL16 from capsids is sent when virions merely bind to cells at 4°C. The internal change was also observed upon binding to immobilized heparin in a manner that requires viral glycoprotein C. This represents the first example of signaling across a viral envelope following receptor binding.

    Original languageEnglish (US)
    Pages (from-to)10429-10435
    Number of pages7
    JournalJournal of virology
    Volume82
    Issue number21
    DOIs
    StatePublished - Nov 2008

    All Science Journal Classification (ASJC) codes

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

    Fingerprint

    Dive into the research topics of 'Structural rearrangement within an enveloped virus upon binding to the host cell'. Together they form a unique fingerprint.

    Cite this