%0 Journal Article %1 Hung:1994fv %A Hung, S L %A Peng, C %A Kostavasili, I %A Friedman, H M %A Lambris, J D %A Eisenberg, R J %A Cohen, G H %D 1994 %J Virology %K imported %N 2 %P 299--312 %R 10.1006/viro.1994.1488 %T The interaction of glycoprotein C of herpes simplex virus types 1 and 2 with the alternative complement pathway. %U http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=8053154&retmode=ref&cmd=prlinks %V 203 %X Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) binds the human complement fragment C3b, but the two proteins differ in their ability to bind C3b on infected cell surfaces. In addition, gC-1, but not gC-2, accelerates the decay of the alternative pathway C3 convertase, thereby affecting later steps of the complement cascade. Previously, we constructed linker insertion and deletion mutants of gC-1 and gC-2 and used transient transfection to express mutant proteins in uninfected cells. In spite of the differences between gC-1 and gC-2, C3b binding was localized to residues within the central portion of both proteins, encompassing the first four cysteines. For gC-1, deletion mutants lacking amino acids 33 to 123 or 367 to 469 or lacking both regions still bound C3b. We recombined these deleted forms of gC-1 into gC-39, an HSV-1 strain lacking the gC gene. The altered forms of gC-1 were incorporated into virions, expressed on the surface of infected cells, and bound C3b. We used these proteins to investigate the structural basis for the inhibitory action of gC-1 on the complement cascade. We found that gC-1 does not inhibit formation of the alternative pathway C3 convertase. This convertase is stabilized by the serum protein properdin. Purified gC-1, but not gC-2, inhibits the binding of properdin to C3b, suggesting that this destabilizes the convertase. The mutant lacking amino acids 367 to 449 was able to inhibit properdin binding to a limited extent when present at high concentrations, although it bound to C3b more weakly than wild-type gC. In contrast, the protein lacking amino acids 33 to 123 was unable to inhibit properdin binding to C3b. Thus, gC-1 contains two structural domains, one for C3b binding, residues 124 to 366, and another, residues 33 to 133, which interferes with properdin binding to C3b.

@article{Hung:1994fv, abstract = {Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) binds the human complement fragment C3b, but the two proteins differ in their ability to bind C3b on infected cell surfaces. In addition, gC-1, but not gC-2, accelerates the decay of the alternative pathway C3 convertase, thereby affecting later steps of the complement cascade. Previously, we constructed linker insertion and deletion mutants of gC-1 and gC-2 and used transient transfection to express mutant proteins in uninfected cells. In spite of the differences between gC-1 and gC-2, C3b binding was localized to residues within the central portion of both proteins, encompassing the first four cysteines. For gC-1, deletion mutants lacking amino acids 33 to 123 or 367 to 469 or lacking both regions still bound C3b. We recombined these deleted forms of gC-1 into gC-39, an HSV-1 strain lacking the gC gene. The altered forms of gC-1 were incorporated into virions, expressed on the surface of infected cells, and bound C3b. We used these proteins to investigate the structural basis for the inhibitory action of gC-1 on the complement cascade. We found that gC-1 does not inhibit formation of the alternative pathway C3 convertase. This convertase is stabilized by the serum protein properdin. Purified gC-1, but not gC-2, inhibits the binding of properdin to C3b, suggesting that this destabilizes the convertase. The mutant lacking amino acids 367 to 449 was able to inhibit properdin binding to a limited extent when present at high concentrations, although it bound to C3b more weakly than wild-type gC. In contrast, the protein lacking amino acids 33 to 123 was unable to inhibit properdin binding to C3b. Thus, gC-1 contains two structural domains, one for C3b binding, residues 124 to 366, and another, residues 33 to 133, which interferes with properdin binding to C3b.}, added-at = {2017-12-08T05:18:19.000+0100}, affiliation = {Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.}, author = {Hung, S L and Peng, C and Kostavasili, I and Friedman, H M and Lambris, J D and Eisenberg, R J and Cohen, G H}, biburl = {https://www.bibsonomy.org/bibtex/2360c9437fb6ecb0c4068a707e435bf44/lambris}, date-added = {2016-04-23T19:10:15GMT}, date-modified = {2017-12-08T04:17:03GMT}, doi = {10.1006/viro.1994.1488}, interhash = {5465acacc773a86b8b5a2b19f1464da9}, intrahash = {360c9437fb6ecb0c4068a707e435bf44}, journal = {Virology}, keywords = {imported}, language = {English}, month = sep, number = 2, pages = {299--312}, pmid = {8053154}, rating = {0}, timestamp = {2017-12-08T05:18:19.000+0100}, title = {{The interaction of glycoprotein C of herpes simplex virus types 1 and 2 with the alternative complement pathway.}}, uri = {\url{papers3://publication/doi/10.1006/viro.1994.1488}}, url = {http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=8053154&retmode=ref&cmd=prlinks}, volume = 203, year = 1994 }