A new report has sounded the alarm about the evolution of avian influenza viruses. Comprehensive genome sequencing shows that the current virus strain is capable of multi-directional infection across species. While the risk from person to person remains low, it is a worrying step as the virus hone its ability to spread.
"This is the first time we have seen evidence of efficient, sustained transmission of highly pathogenic avian influenza H5N1 among mammals," said Diego Diel, corresponding author of the study and director of the Virology Laboratory at Cornell University's Animal Health Diagnostic Center (AHDC).
Cornell University scientists have discovered more about the "spillover" of the highly pathogenic avian influenza (HPIA) H5N12.3.4.4b clade virus, characterized by "significant increases in intensity, frequency, and geographic range" of this zoonotic disease that has killed hundreds of millions of wild and farmed birds since the 2021 epidemic. Currently, outbreaks are reported in every state in the United States, and on every continent except Australia and other parts of Oceania.
It has been observed that the virus is likely transmitted between mammals, and Cornell University scientists have provided evidence of this, with whole-genome sequencing clearly showing that the virus is transmitted between mammals and not just in one direction as is the case with many animal pathogens and hosts. On the bright side, the lab work found no evidence of the 2.3.4.4b lineage mutation, suggesting it had found a shortcut to jumping to humans.
Since highly pathogenic avian influenza first appeared in China in 1996, only 889 people have been infected, but 463 of them died. However, infection has so far been limited to contact with contaminated waste or milk, and although it targets the human respiratory system, there is no evidence that it is spread through the air.
"The concern is that potential mutations may arise that could lead to adaptations in mammals that could spread to humans and potentially spread efficiently among humans in the future," Diel said.
The research team analyzed viral nucleic acids extracted from milk, nasal swabs, whole blood, serum, feces, urine and tissue homogenates from 608 dairy cows on nine farms in the United States. The findings were particularly alarming in that seemingly healthy animals were able to pass the virus to cattle on new farms after being moved across state lines, suggesting that controlling the spread of the virus may be much more difficult than previously thought.
"Our epidemiological investigation, combined with genome sequence and geographical distribution analyses, provides evidence of efficient intra- and interspecific transmission of highly pathogenic avian influenza H5N1 genotype B3.13," the researchers noted. "Shortly after the transfer of apparently healthy lactating cows from Farm 1 to Farm 3, resident animals on Farm 3 developed clinical symptoms consistent with highly pathogenic avian influenza H5N1, providing evidence for non-clinical animal transmission of the virus."
This is concerning because there are currently no "rapid tests" for the COVID-19 virus; as with many pandemics, the most commonly used method currently is the costly and time-consuming quantitative polymerase chain reaction (qRT-PCR) test.
"The bad news is that there are currently no commercial diagnostic tests that specifically detect H5N1," Ayoade Alakija, special envoy for the COVID-19 Access Tools Accelerator, told Al Jazeera in June. "Nucleic acid-based (molecular) tests are currently the gold standard for detecting influenza viruses, but often require laboratory infrastructure to support their use. Even when such infrastructure is available, it may not be fast enough."
In this latest study, the team studied whole viral genome sequences from cows, birds, domestic cats and raccoons, and the results showed that the H5N1 virus spreads in more than one direction (for example, from birds to mammals). Scientists believe that the infected birds - Quiscalus mexicanus and Columbialivia - were likely not infected from other avian species, but through environmental contamination or aerosols in the atmosphere during milking or cleaning at dairy farms.
The data also revealed the virus's "high trophicity" -- or, its ability to infect specific cells -- such that it targets the mammary glands of cows, resulting in sick animals' milk containing high amounts of the virus. (But it is worth noting that pasteurization can kill 100% of viruses).
Erin M. Sorrell, associate professor at the Johns Hopkins Bloomberg School of Public Health in Maryland, explained: "This is a highly pathogenic strain. It has the ability to replicate outside the traditional sites of low-pathogenic influenza: the intestines of poultry; the upper and lower respiratory tracts of humans. Infection with this virus is systemic."
The Cornell team noted that ongoing monitoring of farmed animals is critical, and the USDA has established a free testing program. However, scientists around the world remain vigilant and pay close attention to "surprises" in the virus's mutation blueprint.
"I think this is still a huge problem," World Health Organization chief scientist Jeremy Farrar said in April.
In recent years, the virus has spread to red foxes (Vulpesvulpes), bears (Ursusamericanus), and harbor seals (Phocavitulina). The virus has entered the polar regions, infecting and killing polar bears (Ursusmaritimus), elephant seals (Miroungaleonine) and Antarctic fur seals (Arctocephalusgazella) in the Arctic, as well as gentoo penguins (Pygoscelispapua) in the Antarctic. Last year, two outbreaks occurred in Maine and Washington state in the United States, resulting in the death of a large number of harbor seals, and many domestic cats and a goat (Caprahircus) were also infected.
"Epidemiological and genomic data indicate high efficiency of cow-to-cow transmission after apparently healthy cows from affected farms were transported to a facility in a different state," the Cornell team noted. "These results demonstrate the spread of highly pathogenic avian influenza H5N12.3.4.4b clade viruses at non-traditional interfaces and underscore the ability of viruses to cross species barriers."
In another new study, scientists at the University of North Carolina at Charlotte (UNC) and the Center for Computational Intelligence for Predicting Health and Environmental Risks (CIPHER) found that the H5N1 strain appears to be better at evading antibodies in its host, including those in humans.
Using advanced artificial intelligence and physical modeling techniques to assess transmission and predict future outcomes, the team found that "the virus is constantly evolving to evade our medical defenses." Because of the nature of H5N1 virus transmission, it does not have a central reservoir within one species or location, so it is a real threat to evolve from an epidemic to a pandemic.
"H5-related avian influenza A is an emerging human pathogen, and the pandemic in wildlife has been ongoing for more than two years," said White, an assistant professor of bioinformatics at UNU. "Our predictive research provides a window into the future use of artificial intelligence in the arms race against emerging pathogens."
This type of research, which uses artificial intelligence tools to combine existing modeling and historical data, may be the key to staying one step ahead of the H5N1 virus. If the worst-case scenario occurs, understanding the interactions between viral proteins and antibodies will also be critical to developing an effective vaccine.
The Cornell study was published unedited in the journal Nature, while the UNU study was posted on the bioRxiv preprint server.