Some Antiviral Drugs Demonstrate High Effectiveness Against Bovine H5N1
A recent study published in Nature reports that a highly pathogenic avian influenza (HPAI) H5N1 virus, isolated from the eye of a farm worker infected through contact with dairy cows, proved lethal in mice and ferrets under high-containment laboratory conditions.
The study investigators also found that the virus isolated from the worker, who experienced mild inflammation of the cornea (conjunctivitis), could be transmitted through the air between separated ferrets and might be capable of binding to and replicating in human respiratory tract cells.
The virus isolated from the worker is called huTX37-H5N1 and has a mutation (PB2-E627K) frequently seen in avian influenza viruses that replicate in mammals, typically making virus replication more efficient. These mutations underscore the need for continued monitoring and evaluation of viruses from the current H5N1 outbreak.
Sensitivity to Antiviral Treatments
The study also showed that a bovine H5N1 virus is susceptible to the antiviral drugs favipiravir and baloxavir marboxil (brand name Xofluza) of the polymerase inhibitor class, as well as the neuraminidase inhibitor zanamivir. The virus is less sensitive to oseltamivir (Tamiflu), another neuraminidase inhibitor.
In laboratory experiments, huTX37-H5N1 replicated in human cornea and lung cells. The scientists determined the lethal dose of huTX37-H5N1 as less than 1 plaque-forming unit (PFU) in mice, compared to 31.6 PFU as the lethal dose of a bovine H5N1 virus isolated from the milk of a lactating cow. The huTX37-H5N1 virus also infected each of 15 different mouse tissues tested, with the highest virus levels found in respiratory tissues.
Researchers also infected ferrets with a high dose of huTX37-H5N1. Flu infections in ferrets more closely resemble human flu infections than those in mice. All infected ferrets died within 5 days, and scientists found huTX37-H5N1 virus in all the tissues sampled, with high levels in the respiratory system. In a prior study, the researchers had infected ferrets with a bovine H5N1 virus and, although it caused severe disease, lethality was limited.
To evaluate respiratory transmission, the scientists placed healthy ferrets in cages about 5 centimeters away from ferrets infected one day earlier with one of four decreasing doses of huTX37-H5N1. All directly infected ferrets died within 6 days and, depending on the exposure dose, between 17 percent and 33 percent of the nearby animals became infected via respiratory droplet transmission. These results indicate that a bovine HPAI H5 virus isolated from an infected person can be transmitted among mammals via respiratory droplets, though with limited efficiency.
Observations in Human Cases and Potential Immunity
The authors note that the person infected with the huTX37-H5N1 virus did not develop severe illness. In fact, human cases reported from the current outbreak have mostly experienced conjunctivitis and/or mild respiratory symptoms. The researchers speculate that eye infection with a low dose of bovine H5N1 virus might result in localized conjunctivitis without severe disease in humans. Multiple exposures to seasonal human influenza viruses, they say, might provide people with low levels of protection against currently circulating HPAI H5N1 viruses—though additional study is needed.
In summary, this study characterizes the huTX37-H5N1 isolate, finding that it may be capable of replicating in cells of the respiratory tract in humans, that it is pathogenic in mice and ferrets, and that it is capable of being transmitted by the respiratory route in ferrets. The authors emphasize that “based on these observations, every effort should be made to contain HPAI H5N1 outbreaks in dairy cattle to limit the possibility of further human infections.”
Reference: “A human isolate of bovine H5N1 is transmissible and lethal in animal models” by Chunyang Gu, Tadashi Maemura, Lizheng Guan, Amie J. Eisfeld, Asim Biswas, Maki Kiso, Ryuta Uraki, Mutsumi Ito, Sanja Trifkovic, Tong Wang, Lavanya Babujee, Robert Presler Jr., Randall Dahn, Yasuo Suzuki, Peter J. Halfmann, Seiya Yamayoshi, Gabriele Neumann and Yoshihiro Kawaoka, 28 October 2024, Nature.
DOI: 10.1038/s41586-024-08254-7
Scientists from the University of Wisconsin at Madison led the research with collaborators from Shizuoka and Tokyo Universities and the Research Center for Global Viral Diseases in Japan. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), funded much of the work through its Centers of Excellence for Influenza Research and Response program.
Interview Between Time.news Editor and Avian Influenza Expert
Time.news Editor: Welcome, Dr. Kim. Thank you for joining us today. The implications of the recent study on the H5N1 virus are alarming yet fascinating. Can you start by summarizing the key findings of this research?
Dr. Kim: Thank you for having me. The study published in Nature reports on a highly pathogenic avian influenza (HPAI) H5N1 virus, termed huTX37-H5N1, isolated from a farm worker who interacted with infected dairy cows. In experimental conditions, this virus was shown to be lethal in mice and ferrets. It has mutations that enhance its ability to replicate in mammals, which raises significant concerns about its potential to affect human health.
Time.news Editor: That’s intriguing. What does the mutation PB2-E627K signify for the virus’s replication, especially in mammals?
Dr. Kim: The PB2-E627K mutation is a common feature in avian influenza viruses that helps them more effectively replicate in mammalian hosts. This mutation can potentially bridge the gap between avian and human infections. Its presence in huTX37-H5N1 suggests the need for close monitoring of this virus, as it increases the likelihood of interspecies transmission.
Time.news Editor: Speaking of transmission, what did the study reveal about how the virus spreads between infected and healthy ferrets?
Dr. Kim: The researchers found that ferrets infected with huTX37-H5N1 could transmit the virus through respiratory droplets to nearby healthy ferrets, albeit with limited efficiency. This highlights a critical point: while direct infection is lethal, human-to-human transmission may not be as effective yet. However, this still poses a risk, especially if the virus mutates further.
Time.news Editor: Let’s discuss the antiviral treatments mentioned in the study. How effective are they against H5N1, and what are the implications for public health?
Dr. Kim: The study demonstrated that huTX37-H5N1 is sensitive to antiviral drugs like favipiravir and baloxavir marboxil (Xofluza), as well as zanamivir. However, it showed reduced sensitivity to oseltamivir (Tamiflu), which is widely used in treating influenza. This disparity is crucial for public health, as it emphasizes the importance of developing and stockpiling effective antivirals that can combat H5N1 if it begins to spread more easily among humans.
Time.news Editor: An interesting aspect of the study is the mild symptoms experienced by the infected farm worker. What does this tell us about human cases of H5N1?
Dr. Kim: Indeed, the worker mostly experienced mild conjunctivitis, which is very different from the severe cases typically associated with H5N1. This suggests that low-dose exposures might not always lead to severe illness in humans, but we must be cautious. The presence of such cases might reflect a localized immune response without systemic infection, which could mask the true severity of the virus in varying exposure scenarios.
Time.news Editor: With the recent outbreak of H5N1, what proactive measures should be taken to monitor and control its spread?
Dr. Kim: Continued surveillance in both avian and mammalian populations is essential. Additionally, educating farm workers about safety measures, including the use of personal protective equipment, could prevent initial infections. Rapid response strategies through vaccine development and antiviral stockpiling will be crucial in case of an outbreak in humans.
Time.news Editor: Thank you, Dr. Kim, for your insights. It’s clear that understanding the nuances of this virus is crucial in safeguarding public health. We appreciate your expertise and look forward to following this critical research.
Dr. Kim: Thank you for having me. It’s important to stay informed and prepared as we study these avian viruses.