title: Functional epitopes on porcine endogenous retrovirus envelope protein interacting with neutralizing antibody combining sites.
abstract: Porcine cell and organ transplantation provides promise for maintaining normal physiological conditions in patients with end-stage organ failure. The approach however poses serious risk of transmitting pig pathogens to humans. Among many potential pathogens, porcine endogenous retroviruses (PERV) are of particular concern due to their ubiquitous nature in pigs and capability of infecting human cells. Major antigenic determinants and receptor binding domains on PERV remain unclear until now. Two monoclonal antibodies (mAb), named 8E10 and 7C4 capable of neutralizing PERV infection in HEK293 cells are isolated at an IC(50) of 3.0 and 2.7 microg/ml, respectively, in this work. Epitope location for mAb 8E10 was mapped to amino acids 427-434, residing at the C-terminal region of the gp70 component of type A PERV Env protein. The mAb 8E10 bound directly to the PERV indicating that the epitope is exposed on the virion surface. The mAb 7C4 epitope was assigned to the region comprising amino acids 517-537 on the p15E component of PERV. In contrast to mAb 8E10, the 7C4 mAb bound native PERV inefficiently suggesting that its epitope is accessible only after the virus interacts with its receptor. Finally, both mAbs variable regions were cloned and nucleotide sequence determined. All together, these results reveal that both mAbs 8E10 and 7C4 effectively neutralize PERV infection and may be used as a mean to prevent PERV infection in patients receiving xenotransplantation.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsin Chu, Taiwan, ROC.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Chiang
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Pan
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Chou
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.forename: Shih-Rong
authors.initials: SR
authors.lastname: Wang
authors.forename: Chiou-Ying
authors.initials: CY
authors.lastname: Yang
authors.forename: Hwan-You
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity; D002460:Cell Line; D020077:Endogenous Retroviruses / Q000276:immunology* / Q000378:metabolism; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism; D012192:Retroviridae Infections / Q000821:virology*; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D011991:Receptors, Virus; D014759:Viral Envelope Proteins