Biology subjects

Berhane, Y.

Publications and source records attributed to Berhane, Y..

6 recordsLinked to original sources

bioRxiv2026

Interpreting the WaveSeekerNet model to reveal the evolution and biology of influenza A virus

BackgroundInfluenza A virus (IAV) is a major public health burden, causing seasonal epidemics and occasional pandemics. Its transmission from avian species to mammals and subsequent spread requires adaptive changes in the viral genome. Understanding these molecular adaptations is essential for pandemic preparedness, and machine learning offers a powerful approach to uncover the evolution and biology of IAV. ResultsThis study established a well-calibrated WaveSeekerNet model that accurately predicted the host source across all 8 IAV segments (macro F1-score: 0.9728), significantly improving the reliability of predicted probabilities with calibration errors approaching zero. Model interpretation revealed that avian-adapted IAVs consistently activated G/C content, whereas mammalian-adapted IAVs generally activated A/T content. This distinction was confirmed by codon-level analysis, in which G/C-rich codons were rewarded for the avian hosts and A/T-rich codons for the mammalian hosts. In the feature space learned by WaveSeekerNet, we defined host-adaptive distance to quantify species barriers and proposed it as a risk-assessment metric. We hypothesized the Mammalian Adaptation Zone (MAZ), a zone where the virus is expected to adjust its host-adaptive distance to reach, thereby helping it establish persistent mammalian lineages. The analysis also revealed the Hard Distance of avian-origin viruses (e.g., H5Nx, H9N2), indicating they have not yet established persistent mammalian lineages. Finally, analysis of human H7N9 (2013, China) and non-human mammalian H5Nx (North America) viruses showed that WaveSeekerNet accurately identified key mammalian-adaptive mutations, including PB2-E627K and PB2-D701N. ConclusionsWaveSeekerNet elucidated IAV host-adaptation mechanisms in silico, providing insights into the underlying mechanisms of host adaptation and informing improved surveillance and intervention strategies.

genomics↗

bioRxiv2025

Examining the Survival of A(H5N1) Influenza Virus in Thermised Whole Cow Milk

The recent spillover events of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b to dairy cattle, and high viral shedding in the milk from infected animals, has created concern that milk and dairy products could be a route for human infection. It has been demonstrated that pasteurization is effective in inactivating A(H5N1) in milk. However, multiple dairy products are made with unpasteurized but thermised milk. The aim of this study was to examine whether some conditions commonly used for thermisation are effective against inactivation of A(H5N1) in whole milk. For this purpose, we artificially inoculated whole raw cow milk with 6.5 log10 EID50 A(H5N1) and heated for 15 seconds at 60{degrees}C, 63{degrees}C and 66{degrees}C, the viral infectivity was tested using embryonated chicken eggs. We observed over 4 and 5 log10 reduction in viral infectivity at 60{degrees}C and 63{degrees}C, respectively. The viral infectivity was reduced to below the detection limit at 66{degrees}C. We also calculated the D-values, the time required to reduce the viral titer by one log10, for each treatment and as expected, we observed a decrease in D-values with increasing thermisation temperature. These data demonstrate that thermisation is effective in reducing the viral load and thus they allow for informed risk assessment of A(H5N1) contaminated dairy products made from thermized milk.

microbiology↗

bioRxiv2024

Detection of a reassortant swine- and human-origin H3N2 influenza A virus in farmed mink in British Columbia, Canada

In December 2021, influenza A viruses (IAV) were detected in a population of farmed mink in British Columbia, Canada. Based on genomic sequencing and phylogenetic analysis, these IAVs were subtyped as H3N2s that originated from reassortment of swine H3N2 (clade 1990.4h), human seasonal H1N1 (pdm09), and swine H1N2 (clade 1A.1.1.3). This reassortant has been subsequently observed in swine in several Midwest American states, as well as in swine and turkeys in Ontario, suggesting its spillover into farmed mink in British Columbia was incidental to its broader dissemination in North American swine populations. These detections reaffirm the need for extensive genomic surveillance of IAVs in swine populations to monitor reassortments that might become public health concerns. They also highlight the need for closer surveillance of IAVs in mink to preserve animal health, protect agricultural interests, and monitor potential zoonotic threats.

microbiology↗

bioRxiv2024

Avian influenza virus circulation and immunity in a wild urban duck population prior to and during a highly pathogenic H5N1 outbreak

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses were first detected in St. Johns, Newfoundland, Canada in late 2021, with the virus rapidly spreading across the western hemisphere over the next year. To investigate the patterns of avian influenza virus (AIV) infection and immune responses subsequent to the arrival of H5N1, we sampled the wild urban duck population in St. Johns for a period of 16 months after the start of the outbreak and compared these findings to archived samples. Antibody seroprevalence was relatively stable before the outbreak (2011-2014) at 27.6% and 3.9% for anti-AIV (i.e., NP) and H5-specific antibodies, respectively. During the winter of 2022, AIV-NP and H5-specific antibody seroprevalence both reached 100%, signifying a population-wide infection event. As expected, population-level immunity waned over time, and we found that ducks were seropositive for anti- AIV-NP antibodies for around twice as long as for H5-specific antibodies. The population was H5 seronegative to the latter approximately six months after the initial H5N1 incursion. In late February 2023, H5N1 clade 2.3.4.4b viruses were again detected in the duck population as a result of a second incursion into Newfoundland from Eurasia, which resulted in a second population-wide infection event. We observed a clear relationship of increasing antibody levels with decreasing viral RNA loads that allowed for interpretation of the course of infection and immune response in infected individuals and applied these findings to two cases of resampled ducks to infer infection history. Our study highlights the significance of applying both AIV surveillance and seroprevalence monitoring to provide a better understanding of AIV dynamics in wild populations, which may be crucial following the arrival of 2.3.4.4b H5Nx subtypes to assess the threats they pose to both wild and domestic animals, and to humans.

microbiology↗

bioRxiv2023

Avian influenza viruses in wild birds in Canada following incursion of the highly pathogenic H5N1 virus from Eurasia in 2021/2022

Following detection of novel highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b in Newfoundland, Canada in late 2021, avian influenza surveillance in wild birds was scaled-up across Canada. Herein, we present results of Canadas Interagency Surveillance Program for Avian Influenza in wild birds during the first year (November 2021 - November 2022) following the incursions of HPAIV from Eurasia. Key objectives of the surveillance program were to (i) detect the presence, distribution and spread of HPAIV and other avian influenza viruses (AIVs), (ii) detect wild bird morbidity and mortality associated with HPAIV, (iii) identify the range of wild bird species infected by HPAIV, and (iv) characterize detected AIV. A total of 6,246 sick and dead wild birds were tested, of which 27.4% were HPAIV positive across 12 taxonomic orders and 80 species. Geographically, HPAIV detections occurred in all Canadian provinces and territories, with the highest numbers in the Atlantic and Central flyways. Temporally, peak detections differed across flyways, though the national peak occurred in April 2022. In an additional 11,295 asymptomatic harvested or live captured wild birds, 5.2% were HPAIV positive across 3 taxonomic orders and 19 species. Whole genome sequencing identified HPAIV of Eurasian origin as most prevalent in the Atlantic flyway, along with multiple reassortants of mixed Eurasian and North American origins distributed across Canada, with moderate structuring at the flyway scale. Wild birds were victims and reservoirs of HPAIV H5N1 2.3.4.4b, underscoring the importance of surveillance encompassing samples from sick and dead, as well as live and harvested birds to provide insights into the dynamics and potential impacts of the HPAIV H5N1 outbreak. This dramatic shift in presence and distribution of HPAIV in wild birds in Canada highlights a need for sustained investment in wild bird surveillance and collaboration across One Health partners.

zoology↗

bioRxiv2023

Outbreak of Highly Pathogenic Avian Influenza Virus H5N1 in Seals in the St. Lawrence Estuary, Quebec, Canada

We describe an unusual mortality event caused by a highly pathogenic avian influenza virus (HPAI) H5N1 clade 2.3.4.4b involving harbor (Phoca vitulina) and grey (Halichoerus grypus) seals in the St. Lawrence Estuary, Quebec, Canada. Fifteen (56%) of the seals submitted for necropsy were considered to be fatally infected by H5N1 containing fully Eurasian (EA) or Eurasian/North American genome constellation. Concurrently, presence of large numbers of bird carcasses infected with H5N1 at haul-out sites most likely contributed to the spill-over of infection to the seals. Histologic changes included meningoencephalitis (100%), fibrinosuppurative alveolitis, and multi-organ acute necrotizing inflammation. This is the first report of fatal H5N1 infection in pinnipeds in Canada, raising concerns about the expanding host of this virus, potential for establishment of a marine mammal reservoir, and the public health risks associated with spillover to mammals.

pathology↗