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Highly pathogenic H5N1 avian influenza (HPAI H5N1) viruses occasionally infect, but typically do not transmit, in mammals. In the spring of 2024, an unprecedented outbreak of HPAI H5N1 in bovine herds occurred in the USA, with virus spread within and between herds, infections in poultry and cats, and spillover into humans, collectively indicating an increased public health risk 1 , 2 , 3 – 4 . Here we characterize an HPAI H5N1 virus isolated from infected cow milk in mice and ferrets. Like other HPAI H5N1 viruses, the bovine H5N1 virus spread systemically, including to the mammary glands of both species, however, this tropism was also observed for an older HPAI H5N1 virus isolate. Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways and inefficiently transmitted to exposed ferrets (one of four exposed ferrets seroconverted without virus detection). Bovine HPAI H5N1 virus thus possesses features that may facilitate infection and transmission in mammals. HPAI H5N1 virus isolated from infected cow milk is characterized in mice and ferrets, was inefficiently transmitted in ferrets, and bound to sialic acids expressed in human upper airways, showing features that may facilitate infection in mammals.

Avian Influenza A(H5N1) Infection in a Farm WorkerA highly pathogenic avian influenza A(H5N1) virus infection was identified in a dairy farm worker in Texas. This pathogen has been reported in multiple dairy herds in several states.

Influenza A(H5N1) virus has been found in cow’s milk, and H5N1 genetic material has been identified in the commercial milk supply. In this report, investigators assess the effect of heat inactivation on viability of the virus.

An outbreak of influenza A (H5N1) virus was detected in dairy cows in the United States. We detected influenza A virus sialic acid -α2,3/α2,6-galactose host receptors in bovine mammary glands by lectin histochemistry. Our results provide a rationale for the high levels of H5N1 virus in milk from infected cows.

Tick-borne encephalitis virus (TBEV) causes serious the neurological disease, tick-borne encephalitis (TBE). TBEV can be transmitted to humans by ticks as well as by the alimentary route, which is mediated through the consumption of raw milk products from infected ruminants such as sheep, goats, and cows. The alimentary route of TBEV was recognized in the early 1950s and many important experimental studies were performed shortly thereafter. Nowadays, alimentary TBEV infections are recognized as a relevant factor contributing to the overall increase in TBE incidences in Europe. This review aims to summarize the history and current extent of alimentary TBEV infections across Europe, to analyze experimental data on virus secretion in milk, and to review possible alimentary infection preventive measures.

Examining the persistence of highly pathogenic avian influenza A(H5N1) from cattle and human influenza A(H1N1)pdm09 pandemic viruses in unpasteurized milk revealed that both remain infectious on milking equipment materials for several hours. Those findings highlight the risk for H5N1 virus transmission to humans from contaminated surfaces during the milking process.

Wesselsbron virus (WSLV) is a zoonotic, mosquito-borne orthoflavivirus endemic to sub-Saharan Africa, causing abortions and stillbirths in small ruminants. The life cycle of WSLV involves Aedes mosquitoes and various wildlife and domestic animals. Seminal studies in the 1950s have shown the zoonotic potential of WSLV, notably in accidental infections of laboratory workers exposed to infected material. More recent epidemiological studies suggest the emergence of clade I WSLV strains in peri-domestic and rural areas of western and eastern Africa. The pathobiology of recent clade I WSLV strains is unknown and no virus isolate is available. To address these gaps, we generated a recombinant clade I WSLV SA999 infectious clone (rSA999) by reverse genetics. Subsequently, lactating ewes were inoculated intravenously with the WSLV rSA999 strain or the clade II SAH177 strain in insect-free biocontainment stables. Inoculated ewes developed fever, viremia, and showed high levels of viral RNA at mucosal surfaces, and elevated viral titers in milk. Milk production was reduced, which directly affected the growth of the lambs, particularly within the rSA999 group. The ewes with higher WSLV titers in their milk in each group transmitted the infection to their lambs, which developed fever, prolonged viremia, and virus secretion. All infected animals produced high antibody titers with cross-neutralizing activity against both WSLV strains. Histopathology and blood biochemistry analysis indicated liver damage associated with necrotizing hepatitis lesions and active viral replication in some cases, which was more pronounced in the rSA999 group. Notably, only the SAH177-infected animals exhibited lesions consistent with meningoencephalitis, suggesting that WSLV clade II strains are neurotropic and that clade I strain are more hepatotropic. These findings demonstrate a previously unrecognized mode of vector-free transmission of WSLV that raises significant concerns for public and animal health.

In late 2023 an H5N1 lineage of high pathogenicity avian influenza virus (HPAIV) began circulating in American dairy cattle Concerningly, high titres of virus were detected in cows’ milk, raising the concern that milk could be a route of human infection. Cows’ milk is typically pasteurised to render it safe for human consumption, but the effectiveness of pasteurisation on influenza viruses in milk was uncertain. To assess this, here we evaluate heat inactivation in milk for a panel of different influenza viruses. This includes human and avian influenza A viruses (IAVs), an influenza D virus that naturally infects cattle, and recombinant IAVs carrying contemporary avian or bovine H5N1 glycoproteins. At pasteurisation temperatures of 63 °C and 72 °C, we find that viral infectivity is rapidly lost and becomes undetectable before the times recommended for pasteurisation (30 minutes and 15 seconds, respectively). We then show that an H5N1 HPAIV in milk is effectively inactivated by a comparable treatment, even though its genetic material remains detectable. We conclude that pasteurisation conditions should effectively inactivate H5N1 HPAIV in cows’ milk, but that unpasteurised milk could carry infectious influenza viruses. In response to the emergence of H5N1 influenza A viruses as a novel pathogen of cattle, this study shows that pasteurisation of cows’ milk should effectively inactivate the virus, but that it remains infectious in unpasteurised milk.

In March 2024, clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses were first detected in U.S. dairy cattle. Similar viruses have since caused 70 zoonotic human infections. To assess changes to zoonotic potential, we characterized A(H5N1) clade 2.3.4.4b viruses isolated from cows’ milk and birds. Bovine-derived viruses are lethal in mice and ferrets and transmit to direct but not airborne contact ferrets. All viruses replicate in human bronchial epithelial cells despite preferentially binding avian virus-like receptors. The bovine-derived viruses remain susceptible to FDA-approved antivirals, and they are inhibited by sera from ferrets vaccinated with WHO-recommended candidate vaccine viruses (CVV) or human sera from clade 2.3.4.4c vaccinees. While 2.3.4.4b viruses induce severe disease in mammalian models, they retain many avian virus-like characteristics. Combined, we conclude that the risk of contemporary bovine-derived viruses to humans not in contact with affected animals is low. However, heightened vigilance remains essential to promptly detect and respond to any changes. Bovine H5N1 viruses are lethal in laboratory animals, but they retain avian traits including limited transmission. Their responsiveness to approved antivirals and candidate vaccines lowers human risk, but ongoing surveillance is critically needed.

The hepatitis E virus is a serious health concern worldwide, with 20 million cases each year. Growing numbers of autochthonous HEV infections in industrialized nations are brought on via the zoonotic transmission of HEV genotypes 3 and 4. Pigs and wild boars are the main animal reservoirs of HEV and play the primary role in HEV transmission. Consumption of raw or undercooked pork meat and close contact with infected animals are the most common causes of hepatitis E infection in industrialized countries. However, during the past few years, mounting data describing HEV distribution has led experts to believe that additional animals, particularly domestic ruminant species (cow, goat, sheep, deer, buffalo, and yak), may also play a role in the spreading of HEV. Up to now, there have not been enough studies focused on HEV infections associated with animal milk and the impact that they could have on the epidemiology of HEV. This critical analysis discusses the role of domestic ruminants in zoonotic HEV transmissions. More specifically, we focus on concerns related to milk safety, the role of mixed farming in cross-species HEV infections, and what potential consequences these may have on public health.