Host responses decouple replication rates and pathogen burdens across FMDV strains

Foot-and mouth disease viruses are highly contagious, globally distributed pathogens that can infect a broad range of cloven-hoofed ungulates, including livestock and wild species. Infectious disease dynamics necessarily operate across biological scales: pathogens replicate within hosts; they transmit among hosts, and across host populations. As such, functional changes in the pathogen-host interaction, affecting pathogen vital rates and host immune dynamics can generate cascading effects at molecular to landscape scales. Linking pathogen dynamics across biological scales is thus critical to understanding evolutionary trajectories of host-pathogen systems, and represents a central challenge in disease ecology.

We investigated within-host dynamics and among-host transmission of three strains (SAT1, SAT2, SAT3) of highly contagious, directly transmitted foot-and-mouth disease viruses (FMDVs) in their wildlife reservoir host, African buffalo. We combined data on viral dynamics, innate and adaptive immune responses of buffalo experimentally infected with southern African territories serotypes of FMDV (SAT1, 2, 3) with non-linear ODE models to ask (i) How does the route of infection affect within-host viral and immune dynamics? (ii) How do viral and immune dynamics vary among FMDV strains?; and (iii) Which viral and immune parameters determine viral replication within and transmission among hosts?

Our data show that variation in viral and immune dynamics among serotypes is far more detectable in contact-infected hosts than in needle-infected buffalo. Using data from contact-infected buffalo, we demonstrate two distinct life history patterns in the viral strains we studied. SAT1 and SAT2 replicated rapidly after transmission of a tiny infectious dose, whereas SAT3 required a higher initial dose and followed a slower growth trajectory in the buffalo. SAT2 infections elicited more rapid and effective immune responses by the host than SAT1 and SAT3 infections, resulting in lower within-host production of SAT2. Taken together, these findings indicate that viral fitness within the host is driven by variation in the host’s immune responses to different viral strains, rather than viral life history differences. By contrast, within-host viral life history variation matched patterns of transmission among hosts during acute FMDV infection. In this case, population-level disease transmission may thus be decoupled from pathogen burdens in individual buffalo due to variation in the hosts’ immune responses to different viral strains. As such, selection pressure to increase transmissibility may not be constrained by virulence in this suite of FMD viruses. Future work should include additional viral strains and assess variation in disease transmission from individual hosts to define response functions linking disease dynamic parameters across scales more comprehensively.