July 8, 2024

expert reaction study on features of infection and transmission of bovine H5N1 influenza

A study published in Nature looks at the infectivity and transmission of H5N1 influenza.

Prof Ash Banyard, Virologist, Animal and Plant Health Agency, said:

“The work by Eisfield et al uses well established laboratory models to start to fill some of our gaps in understanding of the potential ability for the newly emerged clade of avian influenza in cattle in the US to transmit to humans.

“The data is robust and both models and approaches used are consistent with earlier studies and support the current thinking that human infection risk from this virus is low.

“This reflects what is being reported from America with only four reported human cases, all of which have been described as having only mild clinical disease with no evidence of onward spread”

Dr Ruth Harvey, Deputy Director of the Worldwide Influenza Centre at the Francis Crick Institute, said:

“Overall, the experimental design for the study is comprehensive, the data has been interpreted well and the authors have reached fair conclusions without speculation. They identify the limitations in that the work was performed on a single strain of the new Bovine influenza virus, and that more work is needed to come to definitive conclusions about the characteristics of Bovine H5N1 influenza.

“There are some novel characteristics of this work compared with other studies, such as demonstrating the ability of the virus to bind to both a2, 3 and a2,6 sialic acid. This is of concern as it suggests a possible increase in the potential of this virus to infect other mammals, including humans, although more research is needed to confirm how this would happen in practice.”

Prof Ian Brown, Group Leader, The Pirbright Institute, said:

“The research provides new information on the possible threat cow flu poses to animal and public health. The study uses models that have been used regularly to assess wider risk including to humans. The results show unconvincing transmissibility within mice (other than to suckling pups from infected mothers) and ferrets but do report systemic infection including of the mammary gland consistent with that seen in cows. The mouse model in particular does not always produce data that can be directly correlated with humans. The work on predicted binding to cells offers new evidence for wider attachment including to cells lining the upper respiratory tract of humans but requires further study to understand the underlying factors. Overall the study findings are not unexpected but this report provides further science insight to an evolving situation, that emphasises the need for strong monitoring and surveillance in affected or exposed populations, both animals and humans to track future risk.”

Dr Ed Hutchinson, Senior Lecturer, MRC-University of Glasgow Centre for Virus Research (MRC CVR), said:

“The ongoing outbreak of H5N1 influenza in American dairy cows was a shock for virologists. It was surprising because cattle were not a known host for this sort of influenza virus. It was also surprising, and alarming, because very large amounts of H5N1 virus are shed into the milk of infected cattle. In some parts of the USA, the remains of H5N1 viruses have been detected in a substantial proportion of the cows’ milk sold to consumers. We normally think of influenza viruses as respiratory viruses (or in birds, viruses of the gut). An influenza virus spreading in milk raises urgent questions, which this important paper from one of the world’s leading influenza research groups does a lot to answer.

“In this paper, the authors used mice and ferrets, two small mammals commonly used to study influenza virus disease in laboratories, to investigate the behaviour of an H5N1 ‘cow flu.’

“First, they returned to a brief experiment they had already published, confirming that H5N1 cow flu in milk can infect animals that consume or inhale that milk. It is very important to note that this risk applies only to unpasteurised ‘raw’ milk – they, and other groups, have already shown that pasteurisation of milk effectively inactivates influenza viruses. However, consuming raw milk in areas affected by the H5N1 outbreak is clearly a very risky thing to do.

“Next, they explained how a virus that entered through the mouth or nose was getting into milk. By comparing infections with cow flu to infections with a highly pathogenic H5N1 bird flu, and with normal seasonal human flu, they found that while the seasonal flu stayed in the respiratory tract, both of the H5N1 viruses spread throughout the bodies of the infected animals. In doing so the viruses invaded multiple organs including the mammary glands. We already knew that one of the things that makes H5N1 influenza viruses so dangerous is their ability to spread beyond the respiratory tract to other organs. Until the virus turned up in an animal we harvested milk from we hadn’t paid much attention to the mammary glands. Now that we’re looking, it seems like spreading into the mammary glands is something that any of these highly pathogenic H5N1 viruses could do. (Seasonal influenza viruses, which generally stay in the respiratory tract, do not do this.)

“Finally, the authors looked at how cow flu is transmitted. Unsurprisingly, they found that infected mouse mothers could pass the virus on to their pups through their milk. Slightly more reassuringly, they found that in ferrets (a model for respiratory transmission), cow flu could not transmit effectively through breathing – in the same experiment, human seasonal flu did spread efficiently. However, there are still some reasons to be concerned here. The Kawaoka group have previously shown that, in principle, H5N1 bird flu viruses can gain the ability to spread through the respiratory route in mammals. In this case, when they compared their cow flu isolate to bird flu they found that it had already begun to gain some of the properties that would be associated with the ability to spread effectively through respiratory infections in humans. To be clear, it does not appear to be doing this yet, and none of the four human cases so far reported have shown signs of onward transmission. However, this new H5N1 influenza virus would be even harder to control, and even more dangerous to humans, if it gained the ability for effective respiratory spread. Although it is good news that cow flu cannot yet do this, these findings reinforce the need for urgent and determined action to closely monitor this outbreak and to try and bring it under control as soon as possible.”

‘Pathogenicity and transmissibility of bovine H5N1 influenza virus’ by Amie J. Eisfeld et al. was published in Nature at 16:00 UK Time on Monday 08 July 2024.

DOI: 10.1038/s41586-024-07766-6

Declared interests

Dr Ed Hutchinson:  Ed Hutchinson is a Senior Lecturer at the MRC-University of Glasgow Centre for Virus Research (CVR). He was not involved in the current study, though he was involved in one of the other studies showing that pasteurisation of milk effectively inactivated influenza viruses. He has received honoraria for work in a steering group of the Centre for Open Science (Open Practices in Influenza Research; 2021-2022) and on an advisory board for Seqirus (2022). He has unpaid positions on the board of the European Scientific Working group on Influenza and other respiratory viruses (ESWI) and as a scientific adviser to PinPoint Medical.

Prof Ian Brown: I lead an UK research consortia that are addressing some (not all) similar questions but with different early results on receptor binding.

Dr Ed Hutchinson: Ed Hutchinson is a Senior Lecturer at the MRC-University of Glasgow Centre for Virus Research (CVR). He was not involved in the current study, though he was involved in one of the other studies showing that pasteurisation of milk effectively inactivated influenza viruses. He has received honoraria for work in a steering group of the Centre for Open Science (Open Practices in Influenza Research; 2021-2022) and on an advisory board for Seqirus (2022). He has unpaid positions on the board of the European Scientific Working group on Influenza and other respiratory viruses (ESWI) and as a scientific adviser to PinPoint Medical.