Deciphering the Unusual Pattern of Bird Flu Symptoms in Cows

In March 2024, the USDA confirmed that dairy cattle in Texas and Kansas had grow to be contaminated with a extremely pathogenic avian influenza H5N1 pressure. Scientists have been monitoring H5N1 infections in wild chook and domesticated poultry populations because the pressure popped up in North America in 2021, however they thought that bovines have been proof against influenza A viruses (IAV).

“[Cow infection] got here as a whole shock,” stated Lars Erik Larsen, a veterinary virologist on the College of Copenhagen. 

In a preprint posted on bioRxiv, which has not undergone peer evaluation, Larsen and his crew measured the distribution of IAV receptors throughout totally different cow tissues looking for a mechanistic clarification for the way cows contracted the chook flu.1 Whereas their preliminary findings helped clarify the signs reported in contaminated cows, in addition they sparked a brand new speculation on whether or not cows are potential IAV mixing vessels for the era of novel flu viruses that would acquire human-to-human transmission

Wild birds are the pure reservoirs for IAV, however mammalian spillovers into pigs, horses, and people have occurred.2 For instance, the IAV H1N1 and H3N2 subtypes originated in wild birds however advanced to routinely flow into in people on a seasonal foundation. Nonetheless, the information of the virus spreading between cows got here out of left subject: Cows expertise outbreaks of influenza D viruses, however  IAV infections are much less widespread, so scientists didn’t take into account them to be inclined hosts for H5N1.3     

Larsen stated that one of the stunning findings coming from the US reviews is that massive quantities of virus are discovered within the milk, however little or no nestles within the respiratory tract. “It looks like this virus in bovines behaves fully otherwise than in different species,” stated Larsen. These findings instructed that the virus might enter and replicate inside cells housed within the udder, however nobody had checked out IAV receptor expression in these tissues. 

To switch their viral genomes, IAV bind to sialic acid (SA) receptors on epithelial cells. One of many principal causes that transmission of IAV from birds to people is low is that avian viruses prefer to enter cells by way of the SA-α2,Three receptor varieties, that are extremely expressed in birds however much less widespread in people.4 With a purpose to bounce these host obstacles and infect people, avian viruses should evolve to bind to SA-α2,6 receptors, the dominant sort in people.

Larsen, whose analysis primarily focuses on avian and swine influenza viruses, beforehand measured the expression of those receptors within the pig nasal mucosa utilizing two totally different plant lectins that bind to both the α2,6 human receptor or the α2,Three avian receptor.5 With instruments for making these measurements already in hand, Larsen and his crew analyzed the expression of those receptors in cow mind, respiratory tract, and mammary gland tissues that have been archived within the freezers within the pathology division of his college’s veterinary faculty. 

Larsen and his crew noticed excessive expression of the α2,Three avian receptor within the bovine mammary glands, offering a rationale for why this virus seems to readily replicate on this tissue. “That may clarify why we discover a lot virus within the milk,” stated Larsen. In addition they discovered some expression of the avian receptor within the respiratory tract however little or no proof of the receptor within the mind, which matches the minimal respiratory or neurological signs noticed in contaminated cows. 

Once they analyzed the info on the human receptor, the crew was stunned to additionally discover excessive expression within the mammary glands, a discovering that introduced pigs to thoughts. 

Pigs present an ideal platform for IAV trying to purchase new hosts. They coexpress each the avian and human receptors of their respiratory tracks. Because of this pigs contaminated with each human and avian flus present these viruses with an area to mingle and swap genome segments to generate new IAV that the human immune system has by no means seen earlier than. This occurred in 2009 when influenza strains of avian, swine, and human origin contaminated a pig, underwent genetic reassortment, and created a novel H1N1 pressure that kicked off the final swine flu pandemic.6 

Though the preliminary proof from Larsen’s group supplies a mechanistic clarification for why H5N1 is showing in dairy cattle milk, what worries some scientists is that it additionally means that cows might be a possible mixing vessel for avian and human IAV. “That’s simply in concept,” stated Larsen. “I don’t assume that the chance may be very excessive.”

Brian Wasik, a virologist at Cornell College who was not concerned within the research, stated that he welcomes the preliminary evaluation on IAV receptor distribution in bovine mammary tissue, which he famous has been restricted within the literature. “A fast dissemination of details about that’s at all times nice and open for the neighborhood to begin constructing hypotheses of how we perceive how influenza is transferring on this specific tissue,” stated Wasik. 

With respect to the “mixing vessel” speculation, Wasik stated, “[They] are good hypotheses and price dialogue and price setting the framework for future analysis. My concern, and what I expressed publicly, is that the priority of different individuals overinterpreting these slender outcomes and transferring clearly past the speculation framework into one thing bigger.”

Not like a protein receptor, which is reworked from a nucleotide sequence by way of transcription and translation, SA is carbohydrate that’s synthesized by enzymatic processes. “There’s a whole lot of heterogeneity and kinetics in that course of, and also you get plenty of totally different chemical variations of those receptors,” stated Wasik. 

These enzymatic processes result in totally different subtypes of the SA-α2,6 receptor: the N-Glycolylneuraminic acid (Neu5Gc) and N-Acetylneuraminic acid (Neu5Ac) types. Neu5Gc is prevalent throughout totally different mammals, however the gene that encodes the enzyme that converts Neu5Ac into Neuro5Gc is absent in humans.7 Wasik famous that Sambucus nigra lectin, the molecule used on this research to detect the presence SA-α2,6, has a broad binding profile and subsequently can not distinguish between these two subtypes. Due to this fact, bovine might not specific the Neu5Ac type of SA-α2,6 that the human influenza strains use to enter cells. 

“The methodology wants much more rigorous verification,” stated Wasik, who famous that he’d prefer to see a deeper dive into the chemistry of the bovine receptors to raised perceive what they seem like and the way influenza binds to them. “I’m certain that these research are coming from this group and quite a few others, however right now we do not need a definitive understanding of what is current in that tissue,” he stated.

Scientists nonetheless want to find out whether or not cow mammary glands are inclined to human IAV. Greater than 70 years in the past, researchers injected cow udders with human influenza virus and noticed viral replication, suggesting that it’s attainable.8 Nonetheless, these have been direct injections and it’s nonetheless unclear if or how human transmission to the mammary glands would happen. Scientists nonetheless don’t know the mode of transmission of the avian virus into cows.  

“There are such a lot of unanswered questions on this bovine an infection,” stated Larsen.

Along with growing the pattern measurement, Larsen wish to look extra carefully on the receptor distribution within the respiratory tract. “What we concern [is] that this virus begins to unfold amongst cows by droplets as a result of then the chance of human publicity will enhance,” stated Larsen. 

“Given these are all hypotheses and we do not know what this virus goes to do subsequent, my suggestion is we stamp it out as shortly as attainable,” stated Wasik. “Whereas we’re involved about human threat and now this new threat to cattle, what we’re seeing is without doubt one of the largest ecological die-offs of avian species and sea mammals and quite a few different totally different spillovers.”


  1. Kristensen C, et al. The avian and human influenza A virus receptors sialic acid (SA)-α2,3 and SA-α2,6 are widely expressed in the bovine mammary gland. bioRxiv. 2024;2024.05.03.592326.
  2. Abdelwhab EM, Mettenleiter TC. Zoonotic animal influenza virus and potential mixing vessel hosts. Viruses. 2023;15(4):980.
  3. Sreenivasan CC, et al. Influenza A in bovine species: A narrative literature review. Viruses. 2019;11(6):561.
  4. Zhao C, Pu J. Influence of host sialic acid receptors structure on the host specificity of influenza viruses. Viruses. 2022;14(10):2141.
  5. Kristensen C, et al. The avian influenza A virus receptor SA-α2,3-Gal is expressed in the porcine nasal mucosa sustaining the pig as a mixing vessel for new influenza viruses. Virus Res. 2024;340:199304.
  6. Trifonov V, et al. Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus. N Engl J Med. 2009;361(2):115-119. 
  7. Chou HH, et al. A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence. Proc Natl Acad Sci U S A. 1998;95(20):11751-11756.
  8. Mitchell CA, et al. Further experiments relating to the propagation of virus in the bovine mammary gland. Can J Comp Med Vet Sci. 1953;17(5):218-222.

Source link


Your email address will not be published. Required fields are marked *