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

David G. Meckes, John W. Wills

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 1 2008

Fingerprint

Virus Attachment
capsid
Capsid
virion
Virion
viruses
receptors
Membranes
cells
herpes simplex
Ethylmaleimide
Herpesviridae
Cell Surface Receptors
heparin
Simplexvirus
Cell Communication
Cysteine
cysteine
Heparin
glycoproteins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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Structural rearrangement within an enveloped virus upon binding to the host cell. / Meckes, David G.; Wills, John W.

In: Journal of virology, Vol. 82, No. 21, 01.11.2008, p. 10429-10435.

Research output: Contribution to journalArticle

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