LACTATE DEHYDROGENASE-ELEVATING VIRUS-REPLICATION PERSISTS IN LIVER, SPLEEN, LYMPH-NODE, AND TESTIS TISSUES AND RESULTS IN ACCUMULATION OF VIRAL-RNA IN GERMINAL-CENTERS, CONCOMITANT WITH POLYCLONAL ACTIVATION OF B-CELLS

Lactate dehydrogenase-elevating virus (LDV) replicates primarily and m ost likely solely in a subpopulation of macrophages in extraneuronal t issues. Infection of mice, regardless of age, with LDV leads to the ra pid cytocidal replication of the virus in these cells, resulting in th e release of large amounts of LDV into the circulation. The infection then progresses into life-long, asymptomatic, low-level viremic persis tence, which is maintained by LDV replication in newly generated LDV-p ermissive cells which escapes all antiviral immune responses. In situ hybridization studies of tissue sections of adult FVB mice revealed th at by 1 day postinfection (p.i.), LDV-infected cells were present in p ractically all tissues but were present in the highest numbers in the lymph nodes, spleen, and skin, In the central nervous system, LDV-infe cted cells were restricted to the leptomeninges. Most of the infected cells had disappeared at 3 days p.i., consistent with the cytocidal na ture of the LDV infection, except for small numbers in lymph node, spl een, liver, and testis tissues. These tissues harbored infected cells until at least 90 days p.i. The results suggest that the generation of LDV-permissive cells during the persistent phase is restricted to the se tissues. The continued presence of LDV-infected cells in testis tis sue suggests the possibility of LDV release in semen and sexual transm ission. Most striking was the accumulation of large amounts of LDV RNA in newly generated germinal centers of lymph nodes and the spleen, Th e LDV RNA was not associated with infected cells but was probably asso ciated with virions or debris of infected, lysed cells. The appearance of LDV RNA in germinal centers in these mice coincided in time with t he polyclonal activation of B cells, which leads to the accumulation o f polyclonal immunoglobulin G2a and low-molecular-weight immune comple xes in the circulation.