title: Coexistence in lactate dehydrogenase-elevating virus pools of variants that differ in neuropathogenicity and ability to establish a persistent infection.
abstract: Neuropathogenic isolates of lactate dehydrogenase-elevating virus (LDV) differ from nonneuropathogenic isolates in their unique ability to infect anterior horn neurons of immunosuppressed C58 and AKR mice and cause paralytic disease (age-dependent poliomyelitis [ADPM]). However, we and others have found that neuropathogenic LDVs fail to retain their neuropathogenicity during persistent infections of both ADPM-susceptible and nonsusceptible mice. On the basis of a segment in open reading frame 2 that differs about 60% between the neuropathogenic LDV-C and the nonneuropathogenic LDV-P, we have developed a reverse transcription-PCR assay that distinguishes between the genomes of the two LDVs and detects as little as 10 50% infectious doses (ID50) of LDV. With this assay, we found that LDV-P and LDV-C coexist in most available pools of LDV-C and LDV-P. For example, various plasma pools of 10(9.5) ID50 of LDV-C/ml contained about 10(5) ID50 of LDV-P/ml. Injection of such an LDV-C pool into mice of various strains resulted in the rapid displacement in the circulation of LDV-C by LDV-P as the predominant LDV, but LDV-C also persisted in the mice at a low level along with LDV-P. We have freed LDV-C of LDV-P by endpoint dilution (LDV-C-EPD). LDV-C-EPD infected mice as efficiently as did LDV-P, but its level of viremia during the persistent phase was only 1/10,000 that observed for LDV-P. LDV-permissive macrophages accumulated and supported the efficient replication of superinfecting LDV-P. Therefore, although neuropathogenic LDVs possess the unique ability to infect anterior horn neurons of ADPM-susceptible mice, they exhibit a reduced ability to establish a persistent infection in peripheral tissues of mice regardless of the strain. The specific suppression of LDV-C replication in persistently infected mice is probably due in part to a more efficient neutralization of LDV-C than LDV-P by antibodies to the primary envelope glycoprotein, VP-3P. Both neuropathogenicity and the higher sensitivity to antibody neutralization correlated with the absence of two of three N-linked polylactosaminoglycan chains on the ca. 30-amino-acid ectodomain of VP-3P, which seems to carry the neutralization epitope(s) and forms part of the virus receptor attachment site.
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis 55455, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: R R
authors.initials: RR
authors.lastname: Rowland
authors.forename: G W
authors.initials: GW
authors.lastname: Anderson
authors.forename: G A
authors.initials: GA
authors.lastname: Palmer
authors.forename: P G
authors.initials: PG
authors.lastname: Plagemann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018174:Arterivirus Infections / Q000821:virology*; D001483:Base Sequence; D004279:DNA, Viral; D005260:Female; D014644:Genetic Variation; D007772:Lactate dehydrogenase-elevating virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000821:virology; D017735:Virus Latency
chemical_list: D004279:DNA, Viral