Immunosignatures as a Prognostic Tool for LCMV Disease Duration in Mice
Ammar Tanveer1, Rustom Antia2, Stephen A. Johnston3, Phillip Stafford3 and Joseph N. Blattman1
ASU Biodesign Center for Immunotherapy, Vaccines and Virotherapy1, Department of Biology, Emory University2, ASU Biodesign Center for Innovations in Medicine3
Lymphocytic Choriomenengitis Virus (LCMV) (family Arenaviridae) is a globally distributed virus found in mice. While most arenavirus species are typically localized to a geographic region, roughly 5-10% of mice worldwide are found to be seropositive for LCMV. LCMV is capable of zoonotic transmission from mice into humans, potentially resulting in severe hemorrhagic fever and complications during pregnancy. However, little is known about the relative role that the duration of infection in mice has on the risk for human transmission. In order to better model LCMV transmission in the wild, as well as to provide a more accurate assessment of human infection risk, we have tested a new method for assessing LCMV infection duration in mice, even after the virus has been eliminated, by measuring antibody binding profiles using a 130,000 random peptide array. We demonstrate the utility of this assay using mice experimentally infected with either a high or low dose of LCMV C-13 in order to establish chronic and acute infections, respectively. Peptide binding patterns of antibodies on the array, termed “immunosignatures”, were compared using serum drawn from mice at day 8 and 45 post infection. Our results show we can accurately assign infection duration at 45 days post infection, even when virus was eliminated from low-dose infected mice. Furthermore, at 8 days post-infection, we were also able in blinded assays to predict which mice would go on to have an acute versus chronic infection. These findings should enable a better understanding of LCMV dynamics and epidemiology in the wild, including providing a more accurate representation of LCMV transmission risk to humans.
Funding was provided by the NIH.