Biology subjects

Fagre, A.

Publications and source records attributed to Fagre, A..

4 recordsLinked to original sources

bioRxiv2026

Detection of diverse coronaviruses, paramyxoviruses, and rhabdoviruses from cave-dwelling bats in Eastern Uganda

Bats harbor a diversity of viruses, some of which have the potential to impact human and livestock health. Caves in Eastern Uganda are commonly inhabited by bats in the genera Rhinolophus, Hipposideros, Myonycteris, and others. Human encroachment into these caves for shelter, hunting, mineral harvesting, and tourism poses a risk of exposure to infectious agents these bats may carry, yet little is known about the viruses present in these bats. From 2021 - 2023, 635 unique bats were captured in caves by mist net, with 69 bats resampled over the study for a total of 706 sampling instances. A total of 1,394 oral and rectal swabs were collected non-destructively and screened using molecular techniques for coronaviruses, paramyxoviruses, rhabdoviruses, flaviviruses, and filoviruses. Of these samples, 399 (56.5%) were collected during the rainy season and 307 (43.5%) during the dry season. Coronavirus RNA was detected in 59/706 (8.36%) of samples from Rhinolophus spp. (n = 35), Hipposideros caffer (n = 12), Myonycteris angolensis (n = 6), and Miniopterus spp. (n = 6). Six bats (0.85%) were positive for paramyxoviruses. Finally, (3 H. caffer, 1 M. angolensis, 1 Rhinolophus spp. and 1 Nycteris thebaica) 3 Rhinolophus bats were positive for rhabdoviruses (0.42%, all Rhinolophus spp.). No samples were positive for filovirus or flavivirus RNA. This project has generated novel data on the association of bat species and different viral strains present in these bats, advancing our knowledge of viral ecology and spillover risk at the human/bat interface.

genomics↗

bioRxiv2025

Investigation of Powassan virus lineage II pathogenesis and neurotropism in mice

Powassan virus (POWV) is an emerging tick-borne flavivirus that causes disease in humans. POWV has considerable genetic and phenotypic diversity, including highly variable replication in vitro and pathogenesis in mice. This study sought to define the extent of variability in pathogenesis within POWV lineage II in mice and investigate possible viral determinants. Relative to other strains, two New York-derived isolates, NY.19.12 and NY.19.32, caused earlier clinical signs and earlier detection of viral RNA (vRNA) in the spleen and brain compared to mice infected with virus derived from a lineage II infectious clone (WI.97.ic). Sequencing revealed these strains share three amino acid substitutions in envelope, NS1, and NS5 compared to other lineage II strains, which were engineered into a mutant infectious clone. At early time points post-infection, clinical signs, vRNA detection in the cerebellum, and viral distribution in the brain were similar between NY.19.12 and the mutant clone, suggesting these mutations may play a role in disease progression and early neuroinvasion. However, NY.19.12 vRNA was detected in the spleen at significantly higher rates compared to both WI.97.ic and the mutant clone, indicating factors other than these mutations are responsible for increased spleen infection. Importantly, this study highlights the complexity of POWV pathogenesis and suggests that POWV lineage II strains have varying disease phenotypes likely driven by multiple genetic differences. ImportanceTick-borne flaviviruses exhibit considerable genetic and phenotypic diversity in nature, influencing their transmission and pathogenesis. Defining the mechanisms of pathogenesis requires understanding how inter-strain variation translates to phenotypic differences in viral dissemination and neuroinvasion. This study demonstrates that even closely related Powassan virus (POWV) lineage II strains display distinct disease phenotypes that are only partially attributable to nonsynonymous consensus mutations within the viral coding sequence. By highlighting the complexity of POWV infection dynamics in mice, these findings provide valuable insights into how POWV lineage II diversity may shape disease progression and severity in humans.

microbiology↗

bioRxiv2020

A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters

The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients.

microbiology↗

bioRxiv2020

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for reverse zoonosis to New World rodents

Coronavirus disease-19 (COVID-19) emerged in November, 2019 in China and rapidly became pandemic. As with other coronaviruses, a preponderance of evidence suggests the virus originated in horseshoe bats (Rhinolophus spp.) and likely underwent a recombination event in an intermediate host prior to entry into human populations. A significant concern is that SARS-CoV-2 could become established in secondary reservoir hosts outside of Asia. To assess this potential, we challenged deer mice (Peromyscus maniculatus) with SARS-CoV-2 and found robust virus replication in the upper respiratory tract, lungs and intestines, with detectable viral RNA for up to 21 days in oral swabs and 14 days in lungs. Virus entry into the brain also occurred, likely via gustatory-olfactory-trigeminal pathway with eventual compromise to the blood brain barrier. Despite this, no conspicuous signs of disease were observed and no deer mice succumbed to infection. Expression of several innate immune response genes were elevated in the lungs, notably IFN, Cxcl10, Oas2, Tbk1 and Pycard. Elevated CD4 and CD8{beta} expression in the lungs was concomitant with Tbx21, IFN{gamma} and IL-21 expression, suggesting a type I inflammatory immune response. Contact transmission occurred from infected to naive deer mice through two passages, showing sustained natural transmission. In the second deer mouse passage, an insertion of 4 amino acids occurred to fixation in the N-terminal domain of the spike protein that is predicted to form a solvent-accessible loop. Subsequent examination of the source virus from BEI Resources indicated the mutation was present at very low levels, demonstrating potent purifying selection for the insert during in vivo passage. Collectively, this work has determined that deer mice are a suitable animal model for the study of SARS-CoV-2 pathogenesis, and that they have the potential to serve as secondary reservoir hosts that could lead to periodic outbreaks of COVID-19 in North America.

microbiology↗