The ecology and epidemiology of Ross River and Murray Valley encephalitis viruses in Western Australia: examples of One Health in Action.

Arboviruses are maintained and transmitted through an alternating biological cycle in arthropods and vertebrates, with largely incidental disease in humans and animals. As such, they provide excellent examples of One Health, as their health impact is inextricably linked to their vertebrate hosts, their arthropod vectors and the environment. Prevention and control requires a comprehensive understanding of these interactions, and how they may be effectively and safely modified. This review concentrates on human disease due to Ross River and Murray Valley encephalitis viruses, the two major arboviral pathogens in Australia. It describes how their pattern of infection and disease is influenced by natural climatic and weather patterns, and by anthropogenic activities. The latter includes human-mediated environmental manipulations, such as water impoundment infrastructures, human movements and migration, and community and social changes, such as urban spread into mosquito larval habitats. Effective interventions need to be directed at the environmental precursors of risk. This can best be achieved using One Health approaches to improve collaboration and coordination between different disciplines and cross-sectoral jurisdictions in order to develop more holistic mitigation and control procedures, and to address poorly understood ecological issues through multidisciplinary research.

A flavivirus signal peptide balances the catalytic activity of two proteases and thereby facilitates virus morphogenesis.

Two cleavages on either side of a signal peptide separating capsid and prM on the nascent flavivirus polyprotein are uniquely regulated, such that cytosolic capsid cleavage triggers signalase cleavage of prM. Here, we show, using two experimental approaches, that this sequential order of cleavages facilitates virus morphogenesis: (i) A Murray Valley encephalitis virus (MVEV) variant, in which both cleavages occurred efficiently and independently of each other, displayed an assembly defect. (ii) Replicon particle assembly was assayed in packaging cells encoding the MVEV structural proteins; bicistronic expression of either mature or membrane-anchored capsid in addition to that of the prM and E proteins showed enhanced particle production in the latter cell line. Taken together, this study demonstrates that efficient flavivirus assembly requires a cleavable transmembrane anchor of C protein and an obligatory order of cleavages at the C-prM junction, both controlled by sequence elements in the prM signal peptide.

Innate resistance to flavivirus infection in mice controlled by Flv is nitric oxide-independent.

Innate resistance to flaviviruses in mice is active in the brain where it restricts virus replication. This resistance is controlled by a single genetic locus, FLV, located on mouse chromosome 5 near the locus encoding the neuronal form of nitric oxide synthase (Nos1). Since nitric oxide (NO) has been implicated in antiviral activity, its involvement in natural resistance to flaviviruses has been hypothesized. Here we present data on NO production before and during flavivirus infection in both brain tissue and peritoneal macrophages from two flavivirus-resistant (FLV(r)) and one congenic susceptible (FLV(s)) mouse strains. This study provides evidence that NO is not involved in the expression of flavivirus resistance controlled by FLV since: (a) there is no difference in brain tissue NO levels between susceptible and resistant mice, and (b) lipopolysaccharide-induced NO does not abrogate the difference in flavivirus replication in peritoneal macrophages from susceptible and resistant mice.