INFECTION OF HUMAN B-LYMPHOCYTES WITH LYMPHOCRYPTOVIRUSES RELATED TO EPSTEIN-BARR-VIRUS

Lymphocryptoviruses (LCVs) naturally infecting Old World nonhuman prim ates are closely related to the human LCV, Epstein-Barr virus (EBV), a nd share similar genome organization and sequences, biologic propertie s, epidemiology, and pathogenesis. LCVs can efficiently immortalize B lymphocytes from the autologous species, but the ability of a given LC V to immortalize B cells from other Old World primate species is varia ble. We found that LCV from rhesus monkeys did not immortalize human B cells, and EBV did not immortalize rhesus monkey B cells. In this stu dy, baboon LCV could not immortalize human peripheral blood B cells bu t could readily immortalize rhesus monkey B cells, Thus, efficient LCV -induced B-cell immortalization across distant Old World primate speci es appears to he restricted by a species-specific block To further cha racterize this species restriction, we first cloned the rhesus monkey LCV major membrane glycoprotein and discovered that the binding epitop e for the EBV receptor, CD21, was highly conserved, Stable infections of human B cells with recombinant amplicons packaged in rhesus monkey or baboon LCV envelopes were also consistent with a species-restricted block occurring after virus binding and penetration, Transient infect ions of human B cells with simian LCV resulted in latent LCV EBNA-2 ge ne expression and activation of cell CD23 gene expression. EBV-immorta lized human B cells could be coinfected with baboon LCV, and the simia n virus persisted and replicated in human B cells, Thus, several lines of evidence indicate that the species restriction for efficient LCV-i nduced B-cell immortalization occurs beyond virus binding and penetrat ion, This has important implications for the study of LCV infection in Old World primate models and for human xenotransplantation where simi an LCVs may be inadvertently introduced into humans.