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The highly pathogenic avian influenza (HPAI) H5N1 virus clade 2.3.4.4b has caused the death of millions of domestic birds and thousands of wild birds in the USA since January 2022 (refs. 1 – 4 ). Throughout this outbreak, spillovers to mammals have been frequently documented 5 – 12 . Here we report spillover of the HPAI H5N1 virus to dairy cattle across several states in the USA. The affected cows displayed clinical signs encompassing decreased feed intake, altered faecal consistency, respiratory distress and decreased milk production with abnormal milk. Infectious virus and viral RNA were consistently detected in milk from affected cows. Viral distribution in tissues via immunohistochemistry and in situ hybridization revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows. Whole viral genome sequences recovered from dairy cows, birds, domestic cats and a raccoon from affected farms indicated multidirectional interspecies transmissions. Epidemiological and genomic data revealed efficient cow-to-cow transmission after apparently healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of the HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface, underscoring the ability of the virus to cross species barriers. Spillover of the highly pathogenic avian influenza H5N1 virus to dairy cattle and the findings of a clinical, pathological and epidemiological investigation in nine affected farms are reported.

Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages.

The spillover of highly pathogenic avian influenza (HPAI) H5N1 virus to dairy cows and shedding of high amounts of infectious virus in milk raised public health concerns. Here, we evaluated the decay and thermal stability spectrum of HPAI H5N1 virus in raw milk. For the decay studies, HPAI H5N1 positive raw milk was incubated at different temperatures and viral titers and the decimal reduction time values ( D -values) were estimated. We then heat-treated HPAI H5N1 virus positive milk using different thermal conditions including pasteurization and thermization conditions. Efficient inactivation of the virus (5-6 logs) was observed in all tested conditions, except for thermization at 50 °C for 10 min. Utilizing a submerged coil system with temperature ramp up times that resemble commercial pasteurizers, we showed that the virus was rapidly inactivated by pasteurization and most thermization conditions. These results provide important insights into the efficacy of thermal conditions and food safety measures utilized in the dairy industry. Infection of dairy cows with highly pathogenic avian influenza H5N1 virus has raised public health concerns. Here, the authors report the stability of H5N1 in raw milk and show that thermal treatment of milk under FDA-approved pasteurization and various thermization conditions efficiently inactivates HPAI H5N1 virus.

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients ( n  = 15). All patients received remdesivir and some also received nirmatrelvir-ritonavir ( n  = 3) or therapeutic monoclonal antibodies ( n  = 4). Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient sequentially treated with nirmatrelvir-ritonavir and remdesivir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo. Here, the authors isolate a SARS-CoV-2 mutant that has developed decreased sensitivity to Paxlovid and remdesivir from an immunocompromised patient, show that drug resistance can be overcome by simultaneous treatment with both drugs in vitro, and demonstrate that the drug resistant virus can efficiently transmit in the hamster model.

Highly pathogenic avian influenza (HPAI) H5N1 virus has been associated with severe mastitis in dairy cows, leading to decreased milk production. Here we investigated the impact of H5N1 virus infection in health and production parameters in an affected dairy herd in Ohio. Clinical disease, which lasted for about three weeks, was recorded in 20.0% (777/3876) of the adult cows. Milk losses of ~900 kg per cow were recorded in affected cows during a 60 day-post-outbreak period. Seroprevalence was 89.4% (570/637) in the herd, with 76.1% (485/637) of seropositive animals being subclinically infected. Clinically affected cows presented an increased risk of death (6 times) and of premature herd removal (3.6 times) when compared to non-clinical cows. Economic losses due to decreased milk production, mortality, and early herd removal were estimated at $950 per clinically affected cow for a total cost of ~$737,500 for the herd during the observation period. Our results demonstrate a production impact lasting at least 60 days post-clinical diagnosis and major financial consequences of HPAI H5N1 virus infection to dairy farms. Highly pathogenic avian influenza H5N1 virus has recently caused outbreaks in dairy cattle herds in the United States. Here, the authors describe the clinical features and associated economic impacts of an outbreak at a farm in Ohio between March and April 2024.

In 2024, 3 domestic cats in California, USA consumed raw milk contaminated with highly pathogenic avian influenza A(H5N1) virus. Fever and neurologic signs developed; 2 cats died. The surviving cat's urine tested positive for H5N1 virus by reverse transcription PCR. Raw dairy products pose a risk to both animal and human health.

Lumpy skin disease (LSD) emerged in Bangladesh in mid-2019, leading to great economic losses for cattle farmers. This study describes the recent occurrence of the LSDV in Bangladesh and examines the clinical manifestation of the disease in local cattle breeds, characteristic epidemiological features, and pathological findings in affected animals. In addition, a full-genome sequencing of two local LSDV isolates was carried out. A total of 565 animals from 88 households were investigated, and 165 samples (skin lesions, saliva, nasal discharge, feces, and milk) were collected for virus detection. Pathology and immunohistochemistry were performed on nodule biopsies. Fever, nodular skin lesions, and swelling of the joints were the most common clinical manifestations. Skin lesions had a higher concentration of viral DNA compared to other sample types and were therefore selected for virus isolation and characterization. Pathology of the LSD skin nodules comprised a granulomatous reaction in the dermis and hypodermis that extended to the surrounding tissues. Development of the skin lesions started with swelling of keratinocytes with cytoplasmic vacuolation, vasculitis, panniculitis, thrombosis, and infarction. Altogether, the LSDV produced transmural, hemorrhagic, necrotizing, proliferative and ulcerative dermatitis. The LSD viral antigen was detected occasionally in the macrophages, epithelial cells, and vascular smooth muscle cells. The complete genome sequence analysis revealed that the two Bangladeshi field strains (BD-V392.1 and BD-V395.1) were distinct from the contemporary field strains and were closely related to the ancestral African Neethling strain. The findings of this study will improve the diagnosis, monitoring, and control of LSD in Bangladesh.

This study aimed to evaluate the seroprevalence and spatial and temporal clustering of SARS-CoV-2 antibodies in household cats within 63 counties in Illinois from October 2021 to May 2023. The analysis followed a stepwise approach. First, in a choropleth point map, we illustrated the distribution of county-level seroprevalence of SARS-CoV-2 antibodies. Next, spatial interpolation was used to predict the seroprevalence in counties without recorded data. Global and local clustering methods were used to identify the extent of clustering and the counties with high or low seroprevalence, respectively. Next, temporal, spatial, and space-time scan statistic was used to identify periods and counties with higher-than-expected seroprevalence. In the last step, to identify more distinct areas in counties with high seroprevalence, city-level analysis was conducted to identify temporal and space-time clusters. Among 1,715 samples tested by serological assays, 244 samples (14%) tested positive. Young cats had higher seropositivity than older cats, and the third quarter of the year had the highest odds of seropositivity. Three county-level space-time clusters with higher-than-expected seroprevalence were identified in the northeastern, central-east, and southwest regions of Illinois, occurring between June and October 2022. In the city-level analysis, 2 space-time clusters were identified in Chicago’s downtown and the southwestern suburbs of Chicago between June and September 2022. Our results suggest that the high density of humans and cats in large cities such as Chicago, might play a role in the transmission and clustering of SARS-CoV-2. Our study provides an in-depth analysis of SARS-CoV-2 epidemiology in Illinois household cats, which will aid in COVID-19 control and prevention.

Avian influenza virus (AIV) remains a huge challenge for poultry production with negative repercussions for micro- and macro-economy and public health in Bangladesh. High (HP) H5N1 and low pathogenicity (LP) H9N2 AIV are currently endemic in poultry, and both have been reported to infect humans sporadically. Multiple virus introductions of different clades of HPAIV H5N1, reassorted genotypes, and on-going diversification of LPAIV H9N2 create a highly volatile virological environment which potentially implicates increased virulence, adaptation to new host species, and subsequent zoonotic transmission. Allotropy of poultry rearing systems and supply chains further increase the risk of virus spreading, which leads to human exposure and fosters the emergence of new potentially pre-pandemic virus strains. Here, we review the epidemiology, focusing on (i) risk factors for virus spreading, (ii) viral genetic evolution, and (iii) options for AIV control in Bangladesh. It is concluded that improved control strategies would profit from the integration of various intervention tools, including effective vaccination, enhanced biosecurity practice, and improved awareness of producers and traders, although widespread household poultry rearing significantly interferes with any such strategies. Nevertheless, continuous surveillance associated with rapid diagnosis and thorough virus characterization is the basis of such strategies.

SARS-CoV-2 has been detected in various animal species, including dogs. While human-to-animal transmission has been documented, the extent and distribution of SARS-CoV-2 exposure in dogs across the United States of America (USA) remain unclear. To address this need, we investigated the seroprevalence of SARS-CoV-2 antibodies in dogs in the USA and scanned for spatial and temporal clusters of high seroprevalence. Serum samples from 953 dogs from 37 states were screened by serological assays, and 58 (6.09%) samples tested positive for SARS-CoV-2 antibodies. The lowest seropositivity was detected in the third quarter of 2021 (1.16%), while the highest was in the third and fourth quarters of 2024 (23.26%). Maps visualized the distribution of seroprevalence, and the Pacific Northwest and Florida had high seroprevalence, while the Northeast and Midwest USA had low seroprevalence. Two significant space–time clusters were identified. The primary cluster in areas in the state of Washington in October 2024, and the secondary cluster in Florida in March 2022. These findings highlight the importance of surveillance to understand SARS-CoV-2 epidemiology in companion animals and its implications for public health.