Neuropathogenicity and susceptibility to immune response are interdependent properties of lactate dehydrogenase-elevating virus (LDV) and correlate with the number of N-linked polylactosaminoglycan chains on the ectodomain of the primary envelope glycoprotein.
We have developed differential RT-PCR methods to distinguish different isolates of LDV and have purified several quasispecies by repeated end point dilution in mice. They fall into two groups, each possessing two or more members. Group A viruses are non-neuropathogenic, highly resistant to in vitro neutralization by antibodies and efficient in establishment of a life-long, persistently viremic infection in mice despite a detectable immune response. Group B viruses, on the other hand, are neuropathogenic, much more sensitive to antibody neutralization and have an impaired ability to establish a high viremia persistent infection in immune competent mice. These properties seem to be interdependent and correlate with the number of N-glycosylation sites on the short (about 30 amino acid long) ectodomain of the primary envelope glycoprotein, VP-3P, which probably is part of the attachment site for the LDV receptor on permissive cells and harbors an epitope(s) reacting with neutralizing antibodies. Group A viruses possess three closely spaced N-linked polylactosaminoglycan chains, whereas group B viruses lack the two N-terminal ones. We postulate that lack of these polylactosaminoglycan chains endows group B viruses with the ability to interact with a receptor on anterior horn neurons resulting in neuropathogenesis. At the same time, it increases an interaction with neutralizing antibodies thus impeding the infection of macrophages newly generated during the persistent phase of infection which is essential for the continued rounds of replication of the virus.
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455, USA.
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Z
Chen
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Li
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Rowland
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Plagemann
D000595:Amino Acid Sequence; D000606:Amino Sugars / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004279:DNA, Viral; D007772:Lactate dehydrogenase-elevating virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology* / Q000502:physiology
D000606:Amino Sugars; D004279:DNA, Viral; D008562:Membrane Glycoproteins; D011134:Polysaccharides; C096091:VP-3 protein, lactate dehydrogenase-elevating virus; D014759:Viral Envelope Proteins; C039448:lactosaminoglycan