Snow, B. A. | bioRxiv Science

bioRxiv2026

Oropouche virus causes acute hepatitis in mice controlled by Type I interferons

Oropouche virus (OROV), a member of the Peribunyaviridae family endemic to South America, is a current public health threat. The recent OROV outbreak driven by a novel reassortant has caused a dramatic increase in cases in 2024 (13,785 in Brazil, versus only 261 from 2015-2022) with sustained levels of transmission in 2025. Previously underreported outcomes have been recognized including miscarriage, microcephaly, encephalitis, and death. OROV lethality in humans has been attributed to severe coagulopathy with liver involvement, and epidemiological data suggests acute hepatitis occurs in mild cases of Oropouche fever, highlighting the underrecognized role of the liver in OROV pathogenesis. We present two discrete mouse models of OROV hepatic disease -- a lethal model that recapitulates the severe coagulopathy seen in fatal human cases and a model of self-resolving acute hepatitis which recapitulates mild human disease. OROV causes focal hepatic necrosis in mice, which progresses to massive necrosis and death when the Type I interferon receptor is antagonized. Additionally, we found a contemporary OROV isolate is less pathogenic in mice than a historic prototypical strain. These studies enhance our understanding of OROV pathogenesis and pave the way for potential therapeutic development and evaluation. ImportanceThe disease burden of Oropouche fever has been underrecognized and underreported, as highlighted by the increased testing seen in the ongoing outbreak. Specifically, the role of the liver in Oropouche virus pathogenesis has been neglected. Given the ongoing outbreak and increase in severe disease manifestations, there is a present need to understand Oropouche virus pathogenesis and test potential therapeutics. The mouse models of Oropouche-induced hepatitis presented here provide a means to understand how Oropouche virus causes liver damage in both a lethal and sublethal context. These models will be useful for the preclinical evaluation of vaccines and therapeutic treatments. Additionally, we compare the pathogenicity of a historical Oropouche virus isolate to a contemporary human isolate in a lethal mouse model. This represents an additional step towards understanding whether the circulating Oropouche virus isolates are uniquely more pathogenic or if increased testing has highlighted previously unreported outcomes.

microbiology↗

bioRxiv2025

Fatal Human H3N8 Influenza Virus has a Moderate Pandemic Risk

In China, low pathogenic avian influenza (LPAI) H3N8 virus is widespread among chickens and has recently caused three zoonotic infections, with the last one in 2023 being fatal. Here we evaluated the relative pandemic risk of this 2023 zoonotic H3N8 influenza virus, utilizing our previously published decision tree. Serological analysis indicated that a large proportion of the human population does not have any cross-neutralizing antibodies against this H3N8 strain. LPAI H3N8 displayed a dual affinity for 2-3 and 2-6 sialic acids and replicated efficiently in human bronchial epithelial cells. Furthermore, we observed H3N8 transmission via direct contact but not aerosols to ferrets with pre-existing H3N2 immunity. Although pre-existing H3N2 immunity resulted in a shortened disease course in ferrets, it did not reduce disease severity or replication in the respiratory tract. This study suggests that this zoonotic H3N8 strain has moderate pandemic potential and emphasizes the continued need for avian influenza surveillance.

microbiology↗

bioRxiv2022

Surface glia predominantly contribute to the development of ALS/FTD in Drosophila model

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by motor neuron degeneration in the primary motor neurons. C9orf72 repeat expansion mutation is the most prevalent genetic causes of ALS/FTD. Due to the complexity of ALS, there has been no successful therapy for the condition. The traditional neurocentric concept of ALS derives in part from the assumption that the degradation of motor neuron (MN) cells in ALS is driven by cell-autonomous mechanisms, however, recent research has focused on the non-cell-autonomous pathogenic mechanisms such as glial, immune cells and blood-brain barriers participate in the degeneration of MNs in ALS. Drosophila melanogaster is widely used as a genetic model for ALS, giving essential mechanistic data on disease onset and development. Using newly developed genetic tools to individually mark each subtype of the adult glial system in the fruit fly, we demonstrate that surface glia are the major glial subtypes for the pathogenesis of C9orf72-mediated ALS/FTD.

pathology↗