Hepatitis C virus modelled as an indirectly transmitted infection highlights the centrality of injection drug equipment in disease dynamics.

The hepatitis C virus (HCV) epidemic often occurs through the persistence of injection drug use. Mathematical models have been useful in understanding various aspects of the HCV epidemic, and especially, the importance of new treatment measures. Until now, however, few models have attempted to understand HCV in terms of an interaction between the various actors in an HCV outbreak-hosts, viruses and the needle injection equipment. In this study, we apply perspectives from the ecology of infectious diseases to model the transmission of HCV among a population of injection drug users. The products of our model suggest that modelling HCV as an indirectly transmitted infection-where the injection equipment serves as an environmental reservoir for infection-facilitates a more nuanced understanding of disease dynamics, by animating the underappreciated actors and interactions that frame disease. This lens may allow us to understand how certain public health interventions (e.g. needle exchange programmes) influence HCV epidemics. Lastly, we argue that this model is of particular importance in the light of the modern opioid epidemic, which has already been associated with outbreaks of viral diseases.

Evolution of increased survival in RNA viruses specialized on cancer-derived cells.

Viruses and other pathogens can diverge in their evolved host-use strategies because of exposure to different host types and conflicts between within-host reproduction and between-host survival. Most host-pathogen studies have emphasized the role of intrahost reproduction in the evolution of pathogen virulence, whereas the role of extra-host survival has received less attention. Here, we examine the evolution of free-living virion survival in RNA virus populations differing in their histories of host use. To do so, we used lineages of vesicular stomatitis virus (VSV) that were experimentally evolved in laboratory tissue culture for 100 generations on cancer-derived cells, noncancerous cells, or alternating passages of the two host types. We observed that free-living survival improved when VSV populations specialized on human epithelial carcinoma (HeLa) cells, whereas this trait was not associated with selection on noncancer cells or combinations of the cell types. We attributed this finding to shorter-lived HeLa monolayers and/or rapid cell-to-cell spread of viruses on HeLa cells in tissue culture, both of which could select for enhanced virus stability between host-cell replenishment. We also showed evidence that increases in virion survival were associated with decreases in virulence, which suggests a trade-off between survival and virulence for the VSV populations on one cell type. Our results shed new light on the causes and consequences of "sit and wait" infection strategies in RNA viruses.