NATURAL ISOLATES OF SIMIAN-VIRUS-40 FROM IMMUNOCOMPROMISED MONKEYS DISPLAY EXTENSIVE GENETIC-HETEROGENEITY - NEW IMPLICATIONS FOR POLYOMAVIRUS DISEASE

Simian virus 40 (SV40) DNAs in brain tissue and peripheral blood monon uclear cells (PBMCs) of eight simian immunodeficiency virus-infected r hesus monkeys with SV40 brain disease were analyzed. We report the det ection, cloning, and identification of five new SV40 strains following a quadruple testing-verification strategy, SV40 genomes with archetyp al regulatory regions (containing a duplication within the G/C-rich re gulatory region segment and a single 72-bp enhancer element) were reco vered from seven animal brains, two tissues of which also contained vi ral genomes with nonarchetypal regulatory regions (containing a duplic ation within the G/C-rich regulatory region segment as well as a varia ble duplication within the enhancer region). In contrast, PBMC DNAs fr om five of six animals had viral genomes with both regulatory region t ypes. It appeared, based on T-antigen variable-region sequences, that nonarchetypal virus variants arose de novo within each animal. The eig hth animal exclusively yielded a new type of SV4O strain (SV40-K661), containing a protoarchetypal regulatory region (lacking a duplication within the G/C-rich segment of the regulatory region and containing on e 72-bp element in the enhancer region), from both brain tissue and PB MCs, The presence of SV40 in PBMCs suggests that hematogenous spread o f viral infection may occur. An archetypal version of a virus similar to SV40 reference strain 776 (a kidney isolate) was recovered from one brain, substantiating the idea that SV40 is neurotropic as well as ki dney-tropic. Indirect evidence suggests that maternal-infant transmiss ion of SV40 may have occurred in one animal. These findings provide ne w insights for human polyomavirus disease.