Oropouche virus efficiently replicates and is immunostimulatory in vivo in nonhuman primate species.

An Oropouche virus (OROV) outbreak occurred in South America in 2024. The pathogenic potential and host immunological response of this emerging virus are largely unknown, as animal models have been poorly explored. We infected nonhuman primate (NHP) species with OROV and followed viral replication dynamics and subsequent innate and adaptive immunological responses. OROV efficiently replicated in pigtail macaques, rhesus macaques, and vervet African green monkeys. OROV also replicated in sabeus African green monkey, albeit at lower levels than other hosts. OROV RNA was detected in plasma and nasal swabs and infection-induced high levels of innate inflammation, type I interferon gene signatures, immunoglobulin M-positive B cell expansion, high titers of neutralizing antibodies, and detectable frequencies of OROV-specific T cells. Prior infection was protective against reinfection up to 524 days post-initial infection, demonstrating possible protective immunity induction against OROV infection. These data suggest that multiple NHP species are appropriate models for OROV infection and the development of therapeutics and vaccinations.