Neuropathogenicity and sensitivity to antibody neutralization of lactate dehydrogenase-elevating virus are determined by polylactosaminoglycan chains on the primary envelope glycoprotein.
Common strains of lactate dehydrogenase-elevating virus (LDV, an arterivirus), such as LDV-P and LDV-vx, are highly resistant to antibody neutralization and invariably establish a viremic, persistent, yet asymptomatic, infection in mice. Other LDV strains, LDV-C and LDV-v, have been identified that, in contrast, are highly susceptible to antibody neutralization and are incapable of a high viremic persistent infection, but at the same time have gained the ability to cause paralytic disease in immunosuppressed C58 and AKR mice. Our present results further indicate that these phenotypic differences represent linked properties that correlate with the number of N-glycosylation sites associated with the single neutralization epitope on the short ectodomain of the primary envelope glycoprotein, VP-3P. The VP-3P ectodomains of LDV-P/vx possess three N-glycosylation sites, whereas those of LDV-C/v lack the two N-terminal sites. We have now isolated four independent neutralization escape variants of neuropathogenic LDV-C and LDV-v on the basis of their ability to establish a high viremic persistent infection in mice. The VP-3P ectodomains of all four variants had specifically regained two N-glycosylation sites concomitant with decreased immunogenicity of the neutralization eptitope and decreased sensitivity to antibody neutralization as well as loss of neuropathogenicity.
Chen
Z
Z
Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
Li
K
K
Plagemann
P G
PG
D000595:Amino Acid Sequence; D000606:Amino Sugars / Q000737:chemistry*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D018174:Arterivirus Infections / Q000473:pathology / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D007772:Lactate dehydrogenase-elevating virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000821:virology*; D009500:Neutralization Tests; D011134:Polysaccharides / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014766:Viremia; D014779:Virus Replication
D000606:Amino Sugars; D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D011134:Polysaccharides; C096091:VP-3 protein, lactate dehydrogenase-elevating virus; D014759:Viral Envelope Proteins; C039448:lactosaminoglycan