JC VIRUS-INFECTION OF HEMATOPOIETIC PROGENITOR CELLS, PRIMARY B-LYMPHOCYTES, AND TONSILLAR STROMAL CELLS - IMPLICATIONS FOR VIRAL LATENCY

The human polyomavirus JC virus (JCV) infects myelin-producing cells i n the central nervous system, resulting in the fatal demyelinating dis ease progressive multifocal leukoencephalopathy (PML). JCV-induced PML occurs most frequently in immunosuppressed individuals, with the high est incidence in human immunodeficiency type I-infected patients, rang ing between 4 and 6% of all AIDS cases, Although JCV targets a highly specialized cell in the central nervous system, infection is widesprea d, dth more than 80% of the human population worldwide demonstrating s erum antibodies. A number of clinical and laboratory studies have now linked the pathogenesis of PML with JCV infection in lymphoid cells. F or example, JCV-infected lymphocytes have been suggested as possible c arriers of virus to the brain following reactivation of a latent infec tion in lymphoid tissues. To further define the cellular tropism assoc iated with JCV, we have attempted to infect immune system cells, inclu ding CD34(+) hematopoietic progenitor cells derived from human fetal l iver, primary human B lymphocytes, and human tonsillar stromal cells, Our results demonstrate that these cell types as well as a CD34(+) hum an cell line, KG-1a, are susceptible to JCV infection, JCV cannot, how ever, infect KG-1, a CD34(+) cell line which differentiates into a mac rophage-like cell when treated with phorbol esters, In addition, perip heral blood B lymphocytes isolated by how cytometry from a PML patient demonstrate JCV infection. These results provide direct evidence that JCV is not strictly neurotropic hut can infect CD34(+) hematopoietic progenitor cells and those cells which have differentiated into a lymp hocytic, but not monocytic, lineage.