COEXISTENCE IN LACTATE DEHYDROGENASE-ELEVATING VIRUS POOLS OF VARIANTS THAT DIFFER IN NEUROPATHOGENICITY AND ABILITY TO ESTABLISH A PERSISTENT INFECTION

Neuropathogenic isolates of lactate dehydrogenase-elevating virus (LDV ) differ from nonneuropathogenic isolates in their unique ability to i nfect anterior horn neurons of immunosuppressed C58 and AKR mice and c ause paralytic disease (age-dependent poliomyelitis [ADPM]). However, we and others have found that neuropathogenic LDVs fail to retain thei r neuropathogenicity during persistent infections of both ADPM-suscept ible and nonsusceptible mice. On the basis of a segment in open readin g frame 2 that differs about 60% between the neuropathogenic LDV-C and the nonneuropathogenic LDV-P, we have developed a reverse transcripti on-PCR assay that distinguishes between the genomes of the two LDVs an d detects as little as 10 50% infectious doses (ID50) of LDV. With thi s 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 disp lacement 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-E PD 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 r eplication of superinfecting LDV-P. Therefore, although neuropathogeni c LDVs possess the unique ability to infect anterior horn neurons of A DPM-susceptible mice, they exhibit a reduced ability to establish a pe rsistent infection in peripheral tissues of mice regardless of the str ain. The specific suppression of LDV-C replication in persistently inf ected 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 antibod y 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.