- Interaction of Glycoproteins H/L from human α-herpesviruses with αvβ integrins
- Massaro, Raffaele <1988>
Subject
- BIO/19 Microbiologia
Description
- Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV) belong to the viral subfamily Alphaherpesvirinae, and are important neurotropic human pathogens. HSV and VZV fuse their envelope with the membrane of the host cell, a process termed cell entry, accomplished by a conserved trio of viral glycoproteins (gB, gH and gL). Host cell receptors mediate viral entry, i.e. nectin1 is recognized by the viral tropism factor gD in HSV, while the host receptor is still elusive in VZV. Integrins are widely distributed adhesion membrane proteins, and give critical contribution to the entry of most human Herpesviruses. αvβ6 or αvβ8 integrins are interchangeable receptors for HSV gH/gL, and they could synchronize fusion exerted by gB with the virion endocytosis they mediate. αvβ6 or αvβ8 integrins modify the glycoprotein machinery of HSV, but the modification they induce on gH/gL heterodimer was never investigated. The results presented here argue in favor of an integrin dependent mechanism which involves the conserved glycoprotein apparatus of HSV and seems to be essential to HSV entry. This mechanism, which also depends on the presence of gB and nectin1-bound gD, entails the dissociation of gL from gH/gL heterodimer, and its release in the media of culture cells upon binding of αvβ6 or αvβ8 integrins receptors. Recent findings disclose both the resemblance between HSV and VZV gH/gL heterodimer structures and the role of integrins of the alpha V family as receptors for VZV entry, a role probably shared with Myelin Associated Glycoprotein (MAG). However, while MAG function in fusion was associated with VZV gB, it was not clarified which glycoprotein(s) was(were) involved in integrin-mediated VZV entry. Data presented here argue in favor of integrin direct binding with a part of the conserved VZV entry machinery, while VZV fusion seems to be the result of more complex interactions.
Date
- 2017-04-18
Type
- Doctoral Thesis
- PeerReviewed
Format
- application/pdf
Identifier
urn:nbn:it:unibo-20657
Massaro, Raffaele (2017) Interaction of Glycoproteins H/L from human α-herpesviruses with αvβ integrins, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare