Interaction between unrelated viruses during in vivo co-infection to limit pathology and immunity

- We show that ECTV/LCMV co-infection results in decreased ECTV viral load and amelioration of ECTV-induced disease in mice.
- We show that IFN-I induction by LCMV is responsible for the increase in survival since co-infection does not rescue IFN-I receptor deficient mice.
- We show CD8 T cell response to LCMV in ECTV co-infected mice are lower compared to mice infected with LCMV alone.

Great progress has been made in understanding immunity to viral infection. However, infection can occur in the context of co-infection by unrelated pathogens that modulate immune responses and/or disease. We have studied immunity and disease during co-infection with two unrelated viruses: Ectromelia virus (ECTV) and Lymphocytic Choriomeningitis virus (LCMV). ECTV infection can be a lethal in mice due in part to the blockade of Type I Interferons (IFN-I). We show that ECTV/LCMV co-infection results in decreased ECTV viral load and amelioration of ECTV-induced disease, likely due to IFN-I induction by LCMV, as rescue is not observed in IFN-I receptor deficient mice. However, immune responses to LCMV in ECTV co-infected mice were also lower compared to mice infected with LCMV alone and potentially biased toward effector-memory cell generation. Thus, we provide evidence for bi-directional effects of viral co-infection that modulate disease and immunity.