Age dependent susceptibility and immune responses to La Crosse virus infection in non-human primates

La Crosse virus (LACV) is a primary cause of pediatric viral encephalitis in the United States but rarely causes disease in adults. We tested whether cynomolgus macaques displayed a similar age-dependent susceptibility to LACV. Immune responses from naïve or LACV infected weanling (9-15 months), juvenile (19-23 months) or adult (> 6 years) animals were measured and infected animals were monitored for disease. Naïve weanling animals had fewer dendritic cells in their blood and weaker induction of IFN-stimulated genes (ISG) and chemokines when PBMCs were stimulated in vitro. While no infected animals developed disease, the weaker innate response in naive weanlings correlated with increased viral RNA in plasma from 2 of 3 infected weanlings out to 7 days post infection (dpi). Activated CD8⁺ T cells and neutralizing antibody proportions were similar amongst all ages. However, CD4⁺ T cells proportions were increased in young animals relative to adults. This suggests the CD4⁺ adaptive response in young animals may be bolstering an initially weak innate response to clear virus. Finally, because macaques were resistant to disease, we infected 3 common marmosets intranasally with LACV. Marmoset were selected due to their susceptibility to viral encephalitis. Although no animals showed disease signs, one animal had evidence of infection in the nasal mucosa out to 23 days with associated vacuolization, edema and immune cell infiltration.