The Flying Flu: Updates On a Mutating Virus
In this piece, we provide an important update on the current outbreak of avian influenza in the United States and abroad.
Introduction
In our last installment of The Flying Flu, we took you through the biology underlying avian influenza and provided some context behind the human cases primarily observed in farm workers. However, recent developments regarding the spread and mutation of this strain have sparked concern among scientists. In this piece, we’ll build off last month’s Thoughts On… issue to discuss the most recent human strain of H5N1 influenza and its potential impact, as well as address some emerging cases of misinformation and harmful theories surrounding the origins of this current outbreak.
News Update
Starting with recent developments in the ongoing outbreak of H5N1 avian influenza in the United States, the virus was recently detected in a pig on an Oregon farm, marking the first occurrence of H5N1 pig infection during this outbreak. While it’s concerning that the virus has caused infection in another animal, the problem arises from the fact that it was a pig specifically. As a refresher from the previous installment of The Flying Flu, there are two primary types of receptors that the influenza virus must bind to in order to enter and infect a cell. One type is predominant in birds, while the other type is present in humans. However, pigs contain both of these receptor types. This means that, if a pig simultaneously becomes infected with an influenza virus from a bird and a human, the virus can “switch” which type of receptor it uses through a process known as recombination. To simplify a complicated process, an infected pig can result in the generation of a modified virus that has the ability to infect humans. The Oregon pig case presents a concern for recombination, and any further spread to pigs must be monitored closely.
The most recent update on human cases brings the national number to 53, with a new case in Oregon and five more in California. One of the California cases occurred in a child with no exposure to sick farm animals, the second U.S. case to contract H5N1 without contact with farm animals. A study released by the CDC earlier this November, however, indicates that there may be more cases than meets the eye. In collaboration with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment, the CDC tested dairy farm workers for the presence of antibodies against the H5N1 virus, which would indicate previous infection with the virus. From the individuals tested, 7% were positive for these specific antibodies, which means they had contracted the virus from working with infected cows. Concerningly, however, half of these individuals did not show any symptoms at the time of infection. This means that many more people may be infected but remain asymptomatic.
While there has been an uptick in U.S. cases of H5N1, the virus has also recently jumped continents. The Dutch government recently reported detection of avian flu on a chicken farm in the Netherlands earlier this November. This has led to a ban on poultry transport by the Dutch government. Additionally, surrounding poultry farms will need to monitor cases in order to control any future spread of the highly pathogenic virus. However, the Netherlands is not the only country to report a new H5N1 infection over the past few weeks.
A Concerning Case in Canada
On November 8th, an adolescent in British Columbia was admitted to the intensive care unit due to symptoms associated with acute respiratory distress syndrome. Following laboratory testing, officials confirmed the first known human case of H5N1 avian influenza in Canada. How the individual acquired the virus, however, continues to remain unclear. The genetic sequence of this virus was isolated and released to scientists, prompting widespread discussion due to the identification of three concerning mutations. When a virus jumps between species, the genetic sequence of the virus can change to adapt to its new host. As the virus replicates rapidly inside the host, mistakes can be made in the replication of its genetic material, naturally giving rise to mutations. While we observe the same principle via gradual adaptations in plants and animals, it occurs on a much shorter time-scale in viruses, presenting possibilities for rapid adaptation.
The first of the mutations identified in the Canadian strain of avian influenza occurred in a gene involved in viral genome replication. Like us, viruses have their own genes–albeit, many fewer–which encode proteins. Influenza, for example, has 17 proteins. One of these proteins, known as polymerase basic or PB2, plays a role in copying the genome of the virus, a necessary step for viral replication. Importantly, for avian influenza viruses, there is one specific part of this protein that, when mutated, can allow the virus to replicate much better in mammals. This mutation (E627K) is present in the Canadian H5N1 strain. For context, the notation of E627K denotes a switch from one amino acid (glutamic acid, abbreviated E) to another (lysine, abbreviated K) at the 627th position within the protein. Even a switch of one single amino acid can affect protein function by increasing its rate of function or the stability of the protein at different temperatures. The mutation that occurred in the influenza PB2 protein indicates that the virus has adapted for replication in mammals, a development that creates particular concern for human infection.
If you recall from our previous issue of The Flying Flu, viruses enter cells by using their surface proteins, or glycoproteins, to bind specific receptors on the cell surface. In the case of influenza virus, this surface protein is known as hemagglutinin, or HA for short. The other two mutations of interest found in the Canadian strain of H5N1 were present in this HA protein–specifically in the region of the protein that makes contact with the cell surface receptor. Both of the mutations occurred at sites possibly involved with increased cell entry. Previous research has demonstrated that one such mutation, E190D, can cause a shift from the avian to mammalian receptor, meaning this strain might enter human cells more readily. The second mutation, on the other hand, is not ideal, but could be worse. A prediction model known as a deep mutational scan showed that the second hemagglutinin mutation, Q226H, does not result in drastic shifts in receptor recognition–however, a slightly different mutation at that site could cause a receptor shift. Taken together, these two hemagglutinin mutations indicate the start of viral adaptation to a different species, moving from infecting bird cells to human cells.
It is still too early to draw conclusions about how this particular H5N1 strain is transmitted and the effects that infection may produce in the body. However, the mutations identified in this strain reveal a concerning reality: this virus is, little by little, adapting to infect humans more readily.
Emerging Misinformation
Time and time again, especially during crisis events like the COVID-19 pandemic, we have seen how misinformation and conspiracy theories have acted to undermine the impactful research being done to understand and respond to the issue at hand. As scientists continue to monitor the current outbreak of avian influenza, we wanted to take the time to debunk some of the rhetoric and misinformation that has gained popularity on social media platforms, including Substack.
A subject of popular debate among conspiracy theorists is the origin of pathogenic viruses. While some conspiracy theories claim viruses do not exist (they do, we’ve seen them), others argue that mutated viruses do not occur naturally and are “released” or “leaked” from labs. These claims in turn beget fear and mistrust of scientists and research institutions–the very people who spend their lives working to find treatments or preventative measures for these viruses. Importantly, these arguments also blatantly disregard a basic fact of biology: mutations. Because viruses replicate so quickly, most do not have the capacity to “proofread” their copied genetic material as effectively, meaning that rapid replication is quite error-prone. Sometimes, these mutations are beneficial for the virus, and this fitness advantage gives it an edge over other strains.
Supporters of “lab leak” conspiracy theories will often try to point at the fact that viruses undergo drastic changes in certain animals as untrue, or as “evidence” of so-called man-made viruses. However, as we discussed earlier, influenza viruses frequently undergo genetic reassortment within pigs because of the presence of both kinds of receptors. This explains the adaptations that we are currently seeing and those that may arise in the future. Let’s be clear: to perpetuate misinformation about the origin of pathogenic viruses and deny decades of research on influenza reassortment is not only harmful, but can also pose obstacles to public understanding of the concerns and precautions needed to limit virus spread.
Questions about the efficacy or role of vaccination abound in this age of rampant misinformation, generating hesitance around the safety and efficacy of vaccination. With the gradual rise in avian influenza cases, some may wonder why the flu vaccine is not offering protection. Current vaccines are tailored to target a limited number of human–not avian–influenza strains that are circulating throughout the population within that given season, as there are many different types of influenza viruses that do not circulate at the same frequency. While efforts to create what is known as a “universal” influenza vaccine are in progress, the rapid mutation rate of influenza makes it difficult to design an effective vaccine. For now, the annual flu vaccines will not offer protection against avian flu. Vaccination is still advised, however, as it can prevent infection with both a human and avian influenza virus at the same time, which would lead to genetic reassortment of the viruses, as we have discussed in pigs. While some vaccines against H5 do exist, these were approved between 2007 and 2020, making them outdated for this current H5N1 strain. Further efforts into H5N1 vaccine design will prove critical, as past cases of drug-resistant strains of avian influenza have been reported.
Another aspect of the situation to keep in mind is that scientists are constantly analyzing and generating new data about factors like transmission, severity of disease, and prevention measures. During the COVID-19 pandemic, the nature of this process drove many conspiracy theorists to discredit scientific advancement, claiming that scientists were “changing their minds.” With any newly emerging disease, it’s important to keep in mind that it will take time to understand how it is evolving and the effects that certain viral or bacterial strains will have on the body. We cannot expect scientists to immediately understand every facet of a new virus, especially given that they can only draw conclusions off of a limited and isolated number of cases that have occurred so far. Portraying researchers as misleading the public only sows confusion and distrust, which makes it more difficult for treatments and preventative measures to be appropriately carried out. In the face of a public health emergency, scientists and public health officials are working overtime to communicate the latest developments in an effort to protect as many people as possible. Attempts to undermine these efforts will only serve to harm the people and institutions behind this work, which can ultimately prevent the development and implementation of life-saving measures.
Conclusion
With ongoing threats on research institutions and the funding necessary to investigate critical facets of emerging viruses, it is more important than ever to disseminate research findings and communicate directly with the public moving forward. We cannot yet say how this virus will continue to change or whether it will pose a serious threat. Additionally, the path to more concrete knowledge about the spread of this virus and the actions needed to mitigate it is a gradual one. We must maintain patience and trust in the experts–scientists, doctors, and public health officials–who are working around the clock to answer these questions. As more cases of H5N1 continue to be identified, sequence isolations will be key in understanding how the virus is evolving. In the meantime, vaccine development and production is underway, as are efforts to understand whether existing treatments are effective against this strain. Rest assured that, with each new case or research finding, How We Talk About Science will make sure to provide you with the most up-to-date information in future editions of The Flying Flu.