Pathogenesis and transmission dynamics of H5N1 influenza virus infecting cattle

Professor Dr. Salah Mahdi Hassan

Professor of poultry diseases and consultant expert for poultry health

22/7/2024

 

Highly virulent H5N1 avian influenza (HPAI H5N1) viruses occasionally infect Mammals, but are usually not transmitted between them. In the spring of 2024, an unprecedented HPAI H5N1 outbreak occurred in cattle herds in the United States, with the virus spreading within and between herds, infecting poultry and cats, and spreading to humans, collectively indicating increased risks to public health.

A series of experiments on highly virulent H5N1 avian influenza (HPAI H5N1) viruses circulating in infected US dairy cows found that viruses in the milk of those cows caused severe disease in mice and ferrets when inoculated by nasal instillation.

 

The virus isolated from H5N1-infected cows binds to both avian and human cellular receptors, but importantly, it is not transmitted efficiently between weasels infected by respiratory instillation

The findings, published in Nature magazine on July 8, 2024, suggest that HPAI H5N1 viruses isolated from currently infected cows may differ from previous HPAI H5N1 viruses and that these viruses may possess characteristics that could facilitate infection and transmission between dairy cows. However, they do not appear to be Currently capable of efficient respiratory transmission between animals or humans

In March 2024, an HPAI H5N1 outbreak was reported among US dairy cattle that spread through herds and led to fatal infections in cats on infected farms, and subsequent spread of infection to poultry, as well as four human infections reported among dairy farm workers. The HPAI H5N1 viruses isolated from infected cows were found to be closely related to the H5N1 viruses that have been circulating in wild birds in North America since late 2021. It appears that over time, those viruses that infected wild birds underwent genetic changes and spread across the continent, causing outbreaks. The disease occurs in wild birds and mammals, with occasional mortality rates and suspected transmission within animal species.

To better understand the characteristics of H5N1 viruses isolated from cows, researchers from the University of Wisconsin-Madison, the Universities of Shizuoka and Tokyo in Japan, and the Veterinary Medical Diagnostic Laboratory at Texas A&M University conducted experiments to determine the ability of HPAI H5N1 viruses isolated from cows to replicate and cause disease in mice and weasels. , which are routinely used in specialized studies of influenza A virus. Notably, weasels are thought to be a good model for understanding potential influenza transmission patterns between humans because they exhibit similar clinical symptoms, immune responses, and respiratory infections as humans.

 

The researchers gave mice doses of HPAI H5N1 influenza via nasal instillation at different doses (5 mice per dose), and the animals were monitored for changes in body weight and the occurrence of deaths over a period of 15 days. The results showed that all the mice that received the high doses died due to infection. And some deaths occurred in the mice that received the average dose, while the mice that received the lowest dose did not witness any loss in body weight and no deaths were recorded.

The researchers also compared the effects of the HPAI H5N1 virus isolated from cows with the Vietnamese H5N1 strain, which is the typical isolate of the H5N1 avian influenza virus infecting humans, and the H1N1 influenza virus, both of which were injected into mice via nasal instillation. Mice that received HPAI H5N1 virus isolated from bovine or Vietnamese avian H5N1 virus experienced high titers of virus in respiratory and non-respiratory organs, including mammary glands and muscle tissue, as well as isolated cases in the eyes. While the H1N1 virus is found only in the respiratory tissues of animals. Weasels infected with HPAI H5N1 virus, isolated from cattle, by nasal instillation showed increased temperature and body weight loss. As with mice, researchers observed high levels of virus in the rodents’ upper and lower respiratory tracts and in other organs. However, unlike mice, the virus was not isolated from the weasel’s blood or muscle tissue.

The study revealed that HPAI H5N1 virus derived from the milk of infected cows may cause severe disease in mice and weasels after oral administration or via respiratory infection, leading to generalized spread of the virus to non-respiratory tissues including the eye, mammary gland, nipple, and/or Muscles

To test whether H5N1 viruses isolated from cows are transmitted between milks via respiratory droplets during coughing and sneezing, researchers infected groups of weasels (four animals per group) with either HPAI H5N1 virus isolated from infected cows and compared them with H1N1 influenza, which is known to be transmitted efficiently via droplets. Respiratory system . One day later, the uninfected weasels were placed in cages next to the cages of the infected animals. Weasels infected with either influenza virus showed clinical signs of disease and high virus titers in nasal swabs collected over several days. As for the weasel groups in the cages next to the infected animals, the study showed that only the weasels that were exposed to the group infected with the H1N1 virus showed signs of clinical illness, which indicates that the cow influenza virus is not transmitted efficiently through respiratory droplets in the weasel.

Normally, avian and human influenza A viruses do not bind to the same receptors on cell surfaces to initiate infection. However, the researchers found that bovine HPAI H5N1 viruses can bind to both human and avian receptors, raising the possibility that the virus has the ability to bind to cells in the human upper respiratory tract.

Overall, the study demonstrates that the newly isolated H5N1 viruses from bovines may differ from HPAI H5N1 viruses previously circulating in birds and some mammals by having localization specificity to human or avian cellular receptors with limited potential for respiratory transmission in weasels.

What concerns us in Iraq today is to submit a recommendation to the veterinary authorities in the country, and here we mean the esteemed veterinary department, to include among its immediate plans a serological survey of cows located in Iraq and throughout the country’s map to initially investigate the extent of the presence of the H5N1 influenza virus in those cows to determine the field reality for cows in Iraq.