Abstract
The early detection of pathogens with epidemic potential is of major importance to public health. Most emerging infections result in dead-end "spillover" events in which a pathogen is transmitted from an animal reservoir to a human but is unable to achieve the sustained human-to-human transmission necessary for a full-blown epidemic. It is therefore critical to determine why only some virus infections are efficiently transmitted among humans whereas others are not. We sought to determine which biological features best characterized those viruses that have achieved sustained human transmission. Accordingly, we compiled a database of 203 RNA and DNA human viruses and used an information theoretic approach to assess which of a set of key biological variables were the best predictors of human-to-human transmission. The variables analyzed were as follows: taxonomic classification; genome length, type, and segmentation; the presence or absence of an outer envelope; recombination frequency; duration of infection; host mortality; and whether or not a virus exhibits vector-borne transmission. This comparative analysis revealed multiple strong associations. In particular, we determined that viruses with low host mortality, that establish long-term chronic infections, and that are nonsegmented, nonenveloped, and, most importantly, not transmitted by vectors were more likely to be transmissible among humans. In contrast, variables including genome length, genome type, and recombination frequency had little predictive power. In sum, we have identified multiple biological features that seemingly determine the likelihood of interhuman viral transmissibility, in turn enabling general predictions of whether viruses of a particular type will successfully emerge in human populations.