Reservoir host immune responses to emerging zoonotic viruses

Abstract

Zoonotic viruses, such as HIV, Ebola virus, coronaviruses, influenza A viruses, hantaviruses, or henipaviruses, can result in profound pathology in humans. In contrast, populations of the reservoir hosts of zoonotic pathogens often appear to tolerate these infections with little evidence of disease. Why are viruses more dangerous in one species than another? Immunological studies investigating quantitative and qualitative differences in the host-virus equilibrium in animal reservoirs will be key to answering this question, informing new approaches for treating and preventing zoonotic diseases. Integrating an understanding of host immune responses with epidemiological, ecological, and evolutionary insights into viral emergence will shed light on mechanisms that minimize fitness costs associated with viral infection, facilitate transmission to other hosts, and underlie the association of specific reservoir hosts with multiple emerging viruses. Reservoir host studies provide a rich opportunity for elucidating fundamental immunological processes and their underlying genetic basis, in the context of distinct physiological and metabolic constraints that contribute to host resistance and disease tolerance.

Figure 1

Reservoir Host Infection and Disease Tolerance A feature of zoonotic infections in an individual natural host may be the tolerance of high pathogen burdens in the absence of substantial deviation from health. Phase plots (adapted from Schneider and Ayres [2008]) illustrating possible infection trajectories following infection to highlight differences between novel and reservoir hosts in the extent of viral replication, viral kinetics, and associated disease burden. Transmission of zoonotic viruses may be more likely in cases in which there are persistently high viral loads or repeated acute infections of reservoir hosts. Within a population of the reservoir host, repeated infections with a pathogen may occur as a result of waning immunological memory within individuals, circulation of diverse strains to which there is minimal cross-reactive immunity, or the introduction of new susceptible individuals (juveniles). To what extent and in which instances features of the immune response in reservoir hosts contribute to pathogen maintenance in a population is an important open question.

Figure 2

Differences in Immune Responses of Reservoir Hosts Impact Disease Tolerance, Infection Outcome, and the Probability of Emergence in Humans Qualitative or quantitative aspects of innate or adaptive immune responses and their cross-talk may differ in reservoir hosts compared to novel hosts, impacting viral replication kinetics, decreasing pathology, and/or increasing the likelihood of transmission. Thus, reservoir host antiviral immunity may be one factor impacting the probability of emergence of a zoonotic virus in humans, in addition to other ecological, evolutionary, or virological risk factors.