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

• Published in: Virology (New York, N.Y.) N.Y.), 2015-10, Vol.484, p.153-162
• Main Authors: McAfee, Megan S, Huynh, Trung P, Johnson, John L, Jacobs, Bertram L, Blattman, Joseph N
• Format: Article
• Language: English
• Subjects: Animals; Arenaviridae Infections - immunology; Arenaviridae Infections - pathology; Arenaviridae Infections - virology; Co-infection; Coinfection - immunology; Coinfection - pathology; Coinfection - virology; Ectromelia virus - immunology; Ectromelia, Infectious - immunology; Ectromelia, Infectious - pathology; Ectromelia, Infectious - virology; ECTV; Female; IFN-I; Immune response; Infectious Disease; Interferon Type I - immunology; LCMV; Lymphocytic choriomeningitis virus - immunology; Mice, Inbred C57BL; Viral Load
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2015.05.021

Abstract 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.