Abstract
Herpesviridae is a large family of DNA viruses divided into three subfamilies: Alpha-, Beta- and Gammaherpesvirinae. The process of herpesvirus transmission is mediated by a range of proteins, one of which is glycoprotein L (gL). Based on our analysis of the solved structures of HSV2 and EBV gH/gL complexes, we propose that Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and Betaherpesvirinae UL130 originate from chemokines. Herpes simplex virus type 2 gL and human cytomegalovirus homolog (UL130) adopt a novel C chemokine-like fold, while Epstein-Barr virus gL mimics a CC chemokine structure. Hence, it is possible that gL interface with specific chemokine receptors during the transmission of Herpesviridae. We conclude that the further understanding of the function of viral chemokine-like proteins in Herpesviridae infection may lead to development of novel prophylactic and therapeutic treatment.
Highlights
As a family of dsDNA viruses, Herpesviridae are known to infect vertebrates, including humans, and cause progression of various contagious diseases, such as orofacial herpes (HSV1), genital herpes (HSV2), chickenpox and shingles (VZV), opportunistic infections (CMV), Kaposi’s sarcoma (KSHV) and mononucleosis (EBV) [1]
Members of the Herpesviridae family have been classified into three distinct subfamilies: Alpha- (HSV1, HSV2, VZV); Beta- (CMV, HHV-6, HHV-7); Gammaherpesvirinae (EBV, KSHV)
Presentation of the hypothesis In our previous report, based on bioinformatic analysis of protein families, we concluded the possibility of a distant homology between Herpesviridae glycoprotein L and chemokines [12]
Summary
As a family of dsDNA viruses, Herpesviridae are known to infect vertebrates, including humans, and cause progression of various contagious diseases, such as orofacial herpes (HSV1), genital herpes (HSV2), chickenpox and shingles (VZV), opportunistic infections (CMV), Kaposi’s sarcoma (KSHV) and mononucleosis (EBV) [1]. Presentation of the hypothesis In our previous report, based on bioinformatic analysis of protein families, we concluded the possibility of a distant homology between Herpesviridae glycoprotein L (gL) and chemokines [12]. Despite the non-conserved cysteine position, based on structural similarity, we propose that gL HSV2 shall be classified as C type chemokine-like protein. Testing the hypothesis Very low sequence similarity between various chemokines and gL prevents any phylogenetic studies of the origin of these protein families from being carried out, and we are unable to justify whether the different topology types. Discussed here glycoproteins are present in viral envelope and mediate virus entry to host cells Their mechanism and function as chemokine-like proteins remains unknown.
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