Replication of Boid Inclusion Body Disease-Associated Arenaviruses Is Temperature Sensitive in both Boid and Mammalian Cells

Boid inclusion body disease (BIDB) is a fatal disease of boid snakes, the etiology of which has only recently been revealed following the identification of several novel arenaviruses in diseased snakes. BIBD-associated arenaviruses (BIBDAV) are genetically divergent from the classical Old and New World arenaviruses and also differ substantially from each other. Even though there is convincing evidence that SISDAV are indeed the etiological agent of SISD, the SISDAV reservoir hosts if any exist besides boid snakes themselves are not yet known. In this report, we use University of Helsinki virus (UHV; a virus that we isolated from a Boa constrictor with SISD) to show that SISDAV can also replicate effectively in mammalian cells, including human cells, provided they are cultured at 30 degrees C. The infection induces the formation of cytoplasmic inclusion bodies (IS), comprised mainly of viral nucleoprotein (NP), similar to those observed in BIBD and in boid cell cultures. Transferring infected cells from 30 degrees C to 37 degrees C ambient temperature resulted in progressive declines in IS formation and in the amounts of viral NP and RNA, suggesting that SISDAV growth is limited at 37 degrees C. These observations indirectly indicate that IS formation is linked to viral replication. In addition to mammalian and reptilian cells, UHV infected arthropod (tick) cells when grown at 30 degrees C. Even though our findings suggest that SISDAV have a high potential to cross the species barrier, their inefficient growth at mammalian body temperatures indicates that the reservoir hosts of SISDAV are likely species with a lower body temperature, such as snakes. IMPORTANCE The newly discovered boid inclusion body disease-associated arenaviruses (BIBDAV) of reptiles have drastically altered the phylogeny of the family Arenavirus. Prior to their discovery, known arenaviruses were considered mainly rodent-borne viruses, with each arenavirus species having its own reservoir host. BIBDAV have so far been demonstrated in captive boid snakes, but their possible reservoir host(s) have not yet been identified. Here we show, using University of Helsinki virus as a model, that these viruses are able to infect mammalian (including human) and arthropod cells. Our results provide in vitro proof of the considerable ability of arenaviruses to cross species barriers. However, our data indicate that BIBDAV growth occurs at 30 degrees C but is inhibited at 37 degrees C, implying that crossing of the species barrier would be hindered by the body temperature of mammalian species.