Glycoprotein G isoforms from some alphaherpesviruses function as broad-spectrum chemokine binding proteins.
Mimicry of host chemokines and chemokine receptors to modulate chemokine activity is a strategy encoded by beta- and gammaherpesviruses, but very limited information is available on the anti-chemokine strategies encoded by alphaherpesviruses. The secretion of chemokine binding proteins (vCKBPs) has hitherto been considered a unique strategy encoded by poxviruses and gammaherpesviruses. We describe a family of novel vCKBPs in equine herpesvirus 1, bovine herpesvirus 1 and 5, and related alphaherpesviruses with no sequence similarity to chemokine receptors or other vCKBPs. We show that glycoprotein G (gG) is secreted from infected cells, binds a broad range of chemokines with high affinity and blocks chemokine activity by preventing their interaction with specific receptors. Moreover, gG also blocks chemokine binding to glycosaminoglycans, an interaction required for the correct presentation and function of chemokines in vivo. In contrast to other vCKBPs, gG may also be membrane anchored and, consistently, we show chemokine binding activity at the surface of cells expressing full-length protein. These alphaherpesvirus vCKBPs represent a novel family of proteins that bind chemokines both at the membrane and in solution.
Bryant
Neil A
NA
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Davis-Poynter
Nick
N
Vanderplasschen
Alain
A
Alcami
Antonio
A
D018138:Alphaherpesvirinae / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D007242:Herpesvirus 1, Bovine / Q000378:metabolism; D004861:Herpesvirus 1, Equid / Q000378:metabolism; D025881:Herpesvirus 5, Bovine / Q000378:metabolism; D006736:Horses; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D016207:Cytokines; D020033:Protein Isoforms; C102256:US4 protein, bovine herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; C083103:glycoprotein G, Equid herpesvirus 1; D006493:Heparin