In a recent publication in the journal Nature, researchers examined the pathogenicity and transmissibility of a highly pathogenic avian influenza virus (HPAI H5N1) found in cow milk among mammals.
HPAI viruses present a global threat to wild birds and poultry, with HPAI H5N1 viruses being particularly worrisome due to their frequent transmission to mammals. In late 2021, the Eurasian strain of H5N1 (clade 2.3.4.4b) was identified in North America sparking an outbreak that persisted through 2024. Cases of spillover and fatalities from this clade have been documented in both land and marine mammals in the United States. The detection of HPAI H5N1 clade 2.3.4.4b virus in severe human cases in Ecuador and Chile further underscores concerns about the pandemic potential of specific HPAI strains.
To assess the public health implications of milk containing the H5N1 virus, researchers conducted experiments showing that oral consumption of milk from a cow infected with highly pathogenic avian influenza H5N1 resulted in rapid onset of symptoms and widespread virus spread in Bagg Albino Laboratory-Bred Mouse/C strain J (BALB/cJ) mice. When repeating the experiment with smaller milk volumes, they observed significant weight loss and detected virus in the lungs, nasal passages, and brain of mice inoculated with 25 μl or 10 μl of infected milk. In contrast, mice inoculated with 25 μl of milk from a healthy cow did not show any symptoms. Mice inoculated with smaller volumes (5 μl and 1 μl) showed milder symptoms and occasional virus replication. Surviving mice did not develop antibodies against the virus.
To evaluate pathogenicity following respiratory exposure, female BALB/cJ mice received varying concentrations of Cow-H5N1 virus, with observations on body weight and survival. The mouse lethal dose 50 (MLD50) was 31.6 PFU, like clade 2.3.4.4b HPAI H5N1 viruses found in minks from Spain, yet higher than that of A/Vietnam/1203/2004 (VN1203)-H5N1, an avian H5N1 strain. Tissue tropism investigations demonstrated widespread infections with Cow-H5N1 and VN1203-H5N1, with significant virus concentrations in respiratory and non-respiratory organs, including mammary glands, teats, and muscle tissues. The Isumi-H1N1 virus was solely detected in respiratory tissues. Similarly, infected ferrets displayed comparable virus replication patterns, exhibiting high titers in both respiratory and non-respiratory organs, although no virus was found in blood or muscle tissues.
Following this, lactating mice were examined for vertical transmission of Cow-H5N1 to their offspring or adult contacts. Lactating females were inoculated and then either reunited with their pups or housed with non-lactating adults. Virus replication occurred in lactating females, and some pups became infected, although no virus was detected in the adult contacts. The virus was found in the mammary glands and milk of certain lactating females, indicating potential vertical transmission through milk.
In a separate experiment involving respiratory droplet transmission in ferrets, it was observed that while Isumi-H1N1 transmitted effectively, Cow-H5N1 did not. However, one exposed ferret exhibited a low positive hemagglutination inhibition (HI) titre, suggesting possible but inefficient transmission. Studies on receptor binding specificity revealed that Cow-H5N1 could bind to both α2,3- and α2,6-linked sialic acids, unlike the avian VN1203-H5N1 virus, suggesting the ability of Cow-H5N1 to potentially bind to cells in the upper respiratory tract of humans.
Highly pathogenic H5N1 influenza viruses typically do not spread efficiently among mammals, and influenza A viruses are seldom found in cattle. However, the ongoing H5N1 outbreak in dairy cows, with spill-over to other mammals, presents significant public health risks and challenges to the dairy industry. While there have been more than 850 human infections, sustained transmission between mammals has not been consistently reported, although recent outbreaks in minks and marine mammals indicate the possibility. This study demonstrated that a bovine H5N1 virus showed limited transmission via respiratory droplets in ferrets, supporting the potential for mammal-to-mammal transmission. Moreover, the virus exhibited a receptor-binding specificity capable of binding to both human and avian receptors, underscoring its potential for causing a pandemic.
Reference:
- Eisfeld AJ, Biswas A, Guan L, Gu C, Maemura T, Trifkovic S, et al. Pathogenicity and transmissibility of bovine H5N1 influenza virus. Nature. 2024 Jul 8;1–3.
- Burrough ER, Magstadt DR, Petersen B, Timmermans SJ, Gauger PC, Zhang J, et al. Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024 – Volume 30, Number 7—July 2024 – Emerging Infectious Diseases journal – CDC. [cited 2024 Jul 13]; Available from: https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article