Elisa Pérez Ramírez
Researcher in the Department of Infectious Diseases and Global Health at the Centre for Animal Health Research CISA-INIA, CSIC
This is a very solid article carried out by a group of recognised prestige in the area of research on avian influenza viruses.
The results are highly relevant for their impact on animal and public health in the context of a very relevant and highly topical health alert: H5N1 avian influenza.
Since the end of 2020, this virus has caused the death of millions of poultry worldwide and hundreds of thousands of wild birds. In fact, we are living through the largest avian influenza epidemic in history. The impact on the poultry industry and wildlife has been devastating. In addition, the virus has become progressively more capable of jumping to mammals, first in the wild (with mass mortalities of marine mammals in South America, for example), then mink in fur farms in Spain and Finland, outbreaks in domestic cats and finally, the most unexpected and probably the most worrying jump: dairy cattle in the United States. This subtype has never before been detected in ruminants, so this is a completely new scenario with many question marks. Since the end of March, when the virus was confirmed in the first herd in Texas, the virus has been spreading unstoppably across the country, affecting 141 farms in 12 states.
This is the context for this study, which attempts to answer some key questions related to the potential of the virus isolated in cows to be transmitted between mammals by different routes.
The authors confirm that the H5N1 virus in cows (belonging to a specific genotype called B3.13) can cause systemic infection in mice. Mice are easily infected both orally (by ingesting milk from infected cows) and intranasally (by inoculating the virus into the nostrils). Infection by both routes causes disease and death in a percentage of mice and the virus is distributed throughout the body, reaching the mammary glands. In fact, the authors confirm that vertical transmission can occur in the mouse model, i.e. a lactating female can transmit the virus to her offspring via milk.
In addition to mice, this study also evaluates the characteristics of infection in ferrets, which is a species commonly used in in vivo research on influenza viruses and is considered a model closer to humans. Intranasal inoculation in this species also caused disease in the animals and the virus managed to reach many organs, including the brain, eye and mammary glands. Airborne transmission between ferrets occurred, but inefficiently because only one of the "contact" animals developed antibodies, although the virus could not be detected in the nasal swabs of this individual.
Another very relevant finding of this study is that they have shown that the virus isolated in cows has a high affinity for the receptors that the virus normally uses to enter avian cells (alpha 2,3) but also for mammalian receptors (alpha 2,6). These receptors are present in the upper respiratory tract of humans, so this particular genotype of H5N1 may be more capable of infecting and transmitting between humans.
In conclusion, the results of this study demonstrate that the H5N1 subtype isolated in cows has a high tropism (affinity) for the mammary glands, where it replicates intensively, and that at least in mice, the offspring of an infected lactating female can become infected by suckling. This is very relevant in terms of food safety implications in cow's milk and as a possible route of mother-to-calf transmission in cow farms.
Furthermore, it is the first time that an avian influenza virus has the ability to bind not only to avian but also to mammalian cell receptors and, albeit inefficiently, can be transmitted by air between ferrets. All these results indicate a high potential for transmission between mammals and thus an increased pandemic potential of this particular subtype.
With this new information, the importance of keeping a close eye on the H5N1 virus is even more evident. It is never good news when a highly pathogenic virus of avian origin adapts to mammals, but in this case the situation is particularly worrying because this is a livestock species with intense interaction with humans. Faced with this risk scenario, it is imperative to support a One Health strategy in which health surveillance is intensified both in cattle and in workers who are in contact with these animals.