TITLE

αvβ6- and αvβ8-Integrins Serve As Interchangeable Receptors for HSV gH/gL to Promote Endocytosis and Activation of Membrane Fusion

AUTHOR(S)
Gianni, Tatiana; Salvioli, Stefano; Chesnokova, Liudmila S.; Hutt-Fletcher, Lindsey M.; Campadelli-Fiume, Gabriella
PUB. DATE
December 2013
SOURCE
PLoS Pathogens;Dec2013, Vol. 9 Issue 12, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Herpes simplex virus (HSV) - and herpesviruses in general - encode for a multipartite entry/fusion apparatus. In HSV it consists of the HSV-specific glycoprotein D (gD), and three additional glycoproteins, gH/gL and gB, conserved across the Herpesviridae family and responsible for the execution of fusion. According to the current model, upon receptor binding, gD propagates the activation to gH/gL and to gB in a cascade fashion. Questions remain about how the cascade of activation is controlled and how it is synchronized with virion endocytosis, to avoid premature activation and exhaustion of the glycoproteins. We considered the possibility that such control might be carried out by as yet unknown receptors. Indeed, receptors for HSV gB, but not for gH/gL, have been described. In other members of the Herpesviridae family, such as Epstein-Barr virus, integrin receptors bind gH/gL and trigger conformational changes in the glycoproteins. We report that αvβ6- and αvβ8-integrins serve as receptors for HSV entry into experimental models of keratinocytes and other epithelial and neuronal cells. Evidence rests on loss of function experiments, in which integrins were blocked by antibodies or silenced, and gain of function experiments in which αvβ6-integrin was expressed in integrin-negative cells. αvβ6- and αvβ8-integrins acted independently and are thus interchangeable. Both bind gH/gL with high affinity. The interaction profoundly affects the route of HSV entry and directs the virus to acidic endosomes. In the case of αvβ8, but not αvβ6-integrin, the portal of entry is located at lipid microdomains and requires dynamin 2. Thus, a major role of αvβ6- or αvβ8-integrin in HSV infection appears to be to function as gH/gL receptors and to promote virus endocytosis. We propose that placing the gH/gL activation under the integrin trigger point enables HSV to synchronize virion endocytosis with the cascade of glycoprotein activation that culminates in execution of fusion.
ACCESSION #
93395289

 

Related Articles

  • Detection of human herpes viruses in patients with chronic and aggressive periodontitis and relationship between viruses and clinical parameters. Das, Sushma; Krithiga G., Shobha Prakash; S., Gopalakrishnan // Journal of Oral & Maxillofacial Pathology (0973029X);May-Aug2012, Vol. 16 Issue 2, p203 

    Background and Aims: Recent microbiological researches have revealed the possible role of human cytomegalovirus (HCMV), Epstein barr virus (EBV), and herpes simplex virus (HSV-1 and HSV-2) in the etiopathogenesis of periodontal diseases. The present pilot study has been undertaken to detect the...

  • Antibody Evasion by a Gammaherpesvirus O-Glycan Shield. Machiels, Bénédicte; Lété, Céline; Guillaume, Antoine; Mast, Jan; Stevenson, Philip G.; Vanderplasschen, Alain; Gillet, Laurent // PLoS Pathogens;Nov2011, Vol. 7 Issue 11, Special section p1 

    All gammaherpesviruses encode a major glycoprotein homologous to the Epstein-Barr virus gp350. These glycoproteins are often involved in cell binding, and some provide neutralization targets. However, the capacity of gammaherpesviruses for long-term transmission from immune hosts implies that in...

  • The Role of Glycoprotein H in Herpesvirus Membrane Fusion. Browne, H. M. // Protein & Peptide Letters;Jul2009, Vol. 16 Issue 7, p760 

    The mechanism by which herpesviruses fuse with cellular membranes to permit virus entry is still relatively poorly understood. This process is proving difficult to unravel, largely due to the fact that multiple viral envelope proteins appear to function in concert to mediate the fusion event....

  • herpesvirus hominis.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1072 

    An encyclopedia entry for "herpesvirus hominis" is presented.

  • HSV.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1096 

    An encyclopedia entry for the medical acronym "HSV," which stands for herpes simplex virus, is presented.

  • Viremia with Herpes Simplex Type 1 in Adults. Naraqi, Sirus; Jackson, George Gee; Jonasson, Olga M. // Annals of Internal Medicine;Aug76, Vol. 85 Issue 2, p165 

    Presents a study which observed adult patients with nonfatal herpes simplex virus Type 1 viremia in the course of one year. Materials and methods; Results; Summary of clinical case reports.

  • LOOK ALIKE LESIONS. Rosen, Ted; Mills, Julie M. // RN;Mar81, Vol. 44 Issue 3, p52 

    Provides information on herpes simplex virus (HSV) infection. When the most serious danger from chronic infection occurs; Danger if the infection remains unsuspected and precautions are not taken; Recommendation of the United States Center for Disease Control on secretion precautions for...

  • lip service. Drury, Kathryn // Vegetarian Times;Oct2000, Issue 278, p100 

    Focuses on herpes simplex type 1 (HSV-1) virus which causes cold sores. Differences between cold sores and canker sores; How the HSV-1 virus is transmitted; Factors which trigger cold sores. INSET: Nip it in the bud.

  • Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. Krummenacher, Claude; Supekar, Vinit M; Whitbeck, J Charles; Lazear, Eric; Connolly, Sarah A; Eisenberg, Roselyn J; Cohen, Gary H; Wiley, Don C; Carf�, Andrea // EMBO Journal;12/7/2005, Vol. 24 Issue 23, p4144 

    Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics