Who acquires infection from whom and how? Disentangling multi-host and multi-mode transmission dynamics in the 'elimination' era

Multi-host infectious agents challenge our abilities to understand, predict and manage disease dynamics. Within this, many infectious agents are also able to use, simultaneously or sequentially, multiple modes of transmission. Furthermore, the relative importance of different host species and modes can itself be dynamic, with potential for switches and shifts in host range and/ or transmission mode in response to changing selective pressures, such as those imposed by disease control interventions. The epidemiology of such multi-host, multi-mode infectious agents thereby can involve a multi-faceted community of definitive and intermediate/secondary hosts or vectors, often together with infectious stages in the environment, all of which may represent potential targets, as well as specific challenges, particularly where disease elimination is proposed. Here, we explore, focusing on examples fromboth human and animal pathogen systems, why and how we should aim to disentangle and quantify the relative importance of multi-host multi-mode infectious agent transmission dynamics under contrasting conditions, and ultimately, how this can be used to help achieve efficient and effective disease control. This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'

Alteration in Superoxide Dismutase 1 Causes Oxidative Stress and p38 MAPK Activation Following RVFV Infection

Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV). RVFV is a category A pathogen that belongs to the genus Phlebovirus, family Bunyaviridae. Understanding early host events to an infectious exposure to RVFV will be of significant use in the development of effective therapeutics that not only control pathogen multiplication, but also contribute to cell survival. In this study, we have carried out infections of human cells with a vaccine strain (MP12) and virulent strain (ZH501) of RVFV and determined host responses to viral infection. We demonstrate that the cellular antioxidant enzyme superoxide dismutase 1 (SOD1) displays altered abundances at early time points following exposure to the virus. We show that the enzyme is down regulated in cases of both a virulent (ZH501) and a vaccine strain (MP12) exposure. Our data demonstrates that the down regulation of SOD1 is likely to be due to post transcriptional processes and may be related to up regulation of TNFα following infection. We also provide evidence for extensive oxidative stress in the MP12 infected cells. Concomitantly, there is an increase in the activation of the p38 MAPK stress response, which our earlier published study demonstrated to be an essential cell survival strategy. Our data suggests that the viral anti-apoptotic protein NSm may play a role in the regulation of the cellular p38 MAPK response. Alterations in the host protein SOD1 following RVFV infection appears to be an early event that occurs in multiple cell types. Activation of the cellular stress response p38 MAPK pathway can be observed in all cell types tested. Our data implies that maintaining oxidative homeostasis in the infected cells may play an important role in improving survival of infected cells