Ability to replicate in the cytoplasm predicts zoonotic transmission of livestock viruses

Understanding viral factors that promote cross-species transmission is important for evaluating the risk of zoonotic emergence. We constructed a database of viruses of domestic artiodactyls and examined the correlation between traits linked in the literature to cross-species transmission and the ability of viruses to infect humans. Among these traits--genomic material, genome segmentation, and replication without nuclear entry--the last is the strongest predictor of cross-species transmission. This finding highlights nuclear entry as a barrier to transmission and suggests that the ability to complete replication in the cytoplasm may prove to be a useful indicator of the threat of cross-species transmission.