Who is Watching the Mink House?

Viral Explorations in the Wild Kingdoms of Nature and Science.

Over the past week the journalism world came alive again to the Avian Flu pandemic. Multiple stories appeared about what is one of the largest world wide episodes of Avian Influenza on record. Although estimates are obviously largely guess work, we are dealing with bird mortality possibly in the hundreds of millions, and encompassing not just domestic farmed birds, but many wild species. It’s one of the factors involved in your $9/doz. eggs, when you can find some. Tremendous attention has been focused on an article just published Eurosurveillence, detailing the rapid spread of Avian Flu through a mink farm in northern Spain, and the premature demise of all the soon to be collars and coats. https://www.eurosurveillance.org/content/10.2807/1560- 7917.ES.2023.28.3.2300001

Just for a very quick review: Influenza viruses have two major proteins which we use to categorize them. The H protein (haemagglutinin) on the surface of the virus latches onto airway receptors, and begins the process of infection by attachment and membrane fusion. It’s analogous to the COVID S protein. There are 18 types H protein, and they confer species specificity. H1, H2, H3 types of Influenza A infect and spread among humans. The bird viruses have H5 or H7. The second protein is the N (neuraminidase) which is vital for viral replication after the initial penetration of the cell. The current strains of Avian Influenza decimating our feathered friends are H5N1. Occasionally mammals, including the Homo sapiens variety, get infected with Avian Influenza strains; but the virus is not well adapted to mammalian physiology, and does not spread from one individual to another. That’s not to say the infection can’t be serious. Over the last few decades, since the current form of bird flu was first recognized in China, just over 800 people have been infected and the mortality rate has been over 50%. The current outbreak of H5N1 in the Spanish mink is unique and concerning because it seems clear that the infection spread quickly from animal to animal with high mortality. Now mink are not people, and perhaps the unique crowded conditions of their confinement played a role in the contagion—but mink have been raised this way for a long time, and Avian Influenza has been around the block too, with plenty of opportunity for intersection on the Venn diagram. More telling, is that the authors of this study sequenced the genome of the viral clade involved, and found that it has a mutation which enables its H protein to attach to mammalian airway receptors (which are different than avian receptors). Why did I start off with a riff on the journalists getting back to the Avian Influenza story? Well “Bird Flu” was the Pandemic most people who consider such stuff have bad dreams about; but then, “Nobody expects the Spanish Inquisition”, COVID or a rogue balloon from China.

How the Spanish virologists recognized the virus infecting the mink had a particular mutation which allows the cross infection with mammals brings me to the next part of the story, Gain of Function research; something which has figured prominently in the news stream over the last three years. We all intuitively know what it is by now: you take a naturally occurring virus and in the laboratory manipulate it to make it more pathogenic, or importantly, make it more transmissible and rapidly spreading. No amount of tortured, arcane, technical jargon can obfuscate what should be clear to any reasonable person. For a little historical background, this topic came front and center about a decade ago when some virologists wanted to understand what it would take for an Avian Influenza H5N1 virus to acquire the ability to infect humans. The references to these papers are following for anyone with more in-depth curiosity. They hyper-mutated the wild type Avian virus and screened millions of mutant combinations, selecting for those that could attach to and infect mammalian cells—then showed that their prize winning mutants could cause airborne infection between ferrets. They of course then characterized the specific mutations allowing the mammalian infection, QED.

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

• Masaki Imai, et al.

Nature volume 486, pages420–428 (2012)

Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets

SANDER HERFST, EEFJE J. A. SCHRAUWEN, [...], AND RON A. M. FOUCHIER,    Science 2012 Jun 22;336(6088):1534-41. doi: 10.1126/science.1213362.

Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets.

These experiments, which were NOT conducted in the highest level bio-containment labs, seemed to be a wake up call. They triggered the US government to put a hold on GOF research and then to establish a protocol by which any experiments of this nature would need to be reviewed by the NIH before being allowed to proceed. In the intervening decade only three proposed sets of experiments were evaluated in this manner, and if you bet the house on there having been many more actually done, which never saw the light of regulatory day, you would go home a winner.

That brings us up to date on a new initiative to address this important issue. The NIH last month convened a panel of experts from multiple fields, called the NSAAB committee, to review the current government protocol for evaluating research into Potential Pandemic Pathogen research. The committee issued a Draft Proposal, and I include a link to this below. There was much disagreement between members of the committee, which basically broke down along the lines of people wanting a greater degree of control over experiments in the name of safety, and other scientists arguing that too many restrictions will stifle the advancement of important science, perhaps hindering a timely response in the face of a new pandemic. Both reasonable sides of a thorny argument. One thing stands out in reading their Draft Proposal; it’s clear that the committee felt the current system of evaluating the risks of such research is totally inadequate. Assuming this group produces a set of guidelines which is acceptable to most people with knowledge of the area, it then goes to the Department of HSS to devise the bureaucratic structure to enforce the recommendations. Of course these rules will apply only in the US—I wonder if the Chinese government will study them.

https://osp.od.nih.gov/wp-content/uploads/2023/01/DRAFT-NSABB-WG-Report.pdf

I don’t remember virologists in the past giving fanciful names to newly discovered viral mutants, but that was in the days before Twitter could give you more name recognition than a Nobel. Orthus (the two headed monster dog from Greek mythology) is the catchy moniker given to a COVID mutant, CH.1.1, which has rapidly become 25% of the COVID in the UK, and a significant (10%) around the world. It’s had some journalistic attention recently, as in “Orthus, the Next Thing to Worry About”. Of course it has more vaccine antibody escape than even XBB.1.5—or why would we even be talking about it—and a nasty mutation found in the dirty Delta variant of summer 2022. To my eye this is just Virus Porn. A look at the CDC COVID variant graphic shows this CH.1.1 has been around since early November in the US and has barely increased at all. To date, no variant destined to cause a significant wave and take over as Top Dog has shown such a lackluster start out-of-the gate, and I believe you can ignore this one. I have frequently alluded to the UK being the canary in the mine for what COVID is coming next, but in this case I think the warm beer and bangers may be interfering. The tiny brown line of 1.6%, just above XBB, is Orthus the monster dog.

On the other hand XBB.1.5 is holding on as the real deal, now surging in the west and other interior portions of the country, and slowly pushing out the earlier variants. It is behaving as expected, not causing a huge wave by itself, but blending into the tail end of the initial winter wave and dragging it out. Overall US new hospitalizations are down, but deaths are still 3500/week. Have a look at the Denver Metro area waste water COVID levels, and note how we are plateaued at a much higher level than the trough which followed last winter’s Omicron BA.1 wave. (Graph thanks to my colleague Greg Craig of Telluride and Denver)

Have a great weekend and keep your eyes on the sky for the Green Comet near Mars. NORAD is now offering rewards for anyone spotting giant Chinese balloons that they miss (extra credit for anyone calling in an ICBM or shooting down a boogey on their own) Also if you see a 3 egg omelette on the menu for less than $18 feel free to give me a call. Thanks for spending time, please pass along to your friends. Comments are free, but your credit card may be billed for responses.