Species selectivity in poxviral complement regulators is dictated by the charge reversal in the central complement control protein modules.
Variola and vaccinia viruses, the two most important members of the family Poxviridae, are known to encode homologs of the human complement regulators named smallpox inhibitor of complement enzymes (SPICE) and vaccinia virus complement control protein (VCP), respectively, to subvert the host complement system. Intriguingly, consistent with the host tropism of these viruses, SPICE has been shown to be more human complement-specific than VCP, and in this study we show that VCP is more bovine complement-specific than SPICE. Based on mutagenesis and mechanistic studies, we suggest that the major determinant for the switch in species selectivity of SPICE and VCP is the presence of oppositely charged residues in the central complement control modules, which help enhance their interaction with factor I and C3b, the proteolytically cleaved form of C3. Thus, our results provide a molecular basis for the species selectivity in poxviral complement regulators.
National Centre for Cell Science, Pune University, Ganeshkhind, Pune 411007, India.
Viveka Nand
VN
Yadav
Kalyani
K
Pyaram
Muzammil
M
Ahmad
Arvind
A
Sahu
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D002417:Cattle; D003179:Complement C3b / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017244:Complement Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000235:genetics / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D008969:Molecular Sequence Data; D013045:Species Specificity; D055672:Static Electricity; D014616:Vaccinia virus / Q000276:immunology* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus; D003179:Complement C3b; D017244:Complement Factor I