Simple diagram of a virus. By domdomegg, Wikimedia Commons
(Click on the following link to listen to an audio version of this blog …. Viruses and the Birth of the Avian Flu
Viruses are very small. They are typically between 10 and 300 nanometers in size. Very few of us have an intuitive sense of what a nanometer is. It is very straightforwardly defined as one billionth (10-9) of a meter, but that really doesn’t give us much perspective on it either. An average cell in your body, which you recognize as being a very small thing in itself, is just under 100 micrometers in diameter (a micrometer is one millionth (10-6) of a meter). Without dwelling on the math, by volume, one of your average body cells is a hundred million to a billion times bigger than a virus! So cells are small, but viruses are REALLY small!
Viruses are extremely simple. They have a core of a nucleic acid (either DNA or RNA) surrounded by a “capsid” made up of proteins that are then, in some viruses, further surrounded by “envelopes” of lipids that are studded with very specific glycoproteins.
Viral nucleic acids typically encode the information for 30 or 40 genes, and these genes represent the information needed for the synthesis of a variety of molecules including the components of the viral capsid and envelope. Viruses must utilize the metabolic machinery of a living cell to replicate themselves since they lack both energy generating systems and also the ribosomes needed for protein synthesis.
Diagram by B. Taylor. Wikimedia Commons
Of the 7000 or so species of viruses that have been described, only 200 affect humans. Viruses have to enter cells in order for their genes to be able to hijack the cell’s metabolic machinery and program it to make more viruses. Entering a cell is not an easy thing even for something as small as a virus. On a cell’s plasma membrane are numerous proteins that act as enzymes or channels or transporters for ions and molecules. Often, these membrane proteins are the doorways by which a virus enters a cell. The virus, though, has to fit very precisely into these membrane proteins in order to pass through them. Viruses that can pass through one species’ type of membrane protein might not fit through a similar protein of a different species. So, particular viruses usually only infect certain host species!
Flu viruses are very common, disease causing entities that can affect almost any species of birds or mammals. There are four types of influenza viruses: Types A, B, C and D. Only Types A and B can affect humans, and Type A is the most common influenza virus involved in human disease. Many other species of birds and mammals can also be affected by Type A influenza viruses, although I said above, usually each virus is relatively specific for a particular host species.
Flu virus. Diagram by Young and Lee. Iimedia Commons
The structure of a Type A influenza virus consists of eight individual RNA molecules that are each wrapped by capsid proteins. These RNA’s are grouped together and further wrapped with more matrix proteins and a phospholipid bilayer envelope. The envelope has two major glycoproteins on it: hemagglutinin (H) and neuraminidase (N).
Hemagglutinin (H) makes up 80% of the viral surface glycoproteins. It functions to match up with surface glycoproteins on host cells and, thus, allow the virus to attach itself to a potential host cell. The H’s, then, are critical in the initial steps of a virus matching up to a potential host. Specifically, host cell glycoproteins with sialic acid groups serve as the attachment points for the H glycoproteins. There are 16 types of H glycoproteins.
Neuraminidase (N) makes up the remaining 20% of a virus’s surface glycoproteins. Neuraminidase acts to remove sialic acid molecules from a newly synthesized virus’s envelope as it leaves its host cell. This keeps the emerging viral particles from clumping together via their own H glycoproteins. Some N’s can also alter a host organism’s immune functions and can have impacts on interferon production and activity. There are nine types of N glycoproteins.
The strains of the Type A Influenza virus are classified according to the specific types of H and N glycoproteins that they possess. For example, “Spanish flu” (1918) is H1N1, “Asian flu” (1957) is H2N2, “Hong Kong flu” (1968) is H3N2, “swine flu” (2009) is also H1N1, and avian flu (1996 to present day) is H5N1.
TEM of avian flu virus (H1N5). Photo by CDC. Public Domain
H5N1 is defined as a “highly pathogenic avian influenza” (HPAI). It causes very serious disease in domesticated birds (i.e. “poultry”) and also certain types of wild birds (waterbirds like ducks, geese and swans, shorebirds, and hawks, eagles, falcons, owls, crows, vultures). These HPAI’s are seldom observed in the types of birds that frequent backyards and backyard bird feeders (robins, cardinals, blue jays, house finches, sparrows etc.), so throughout this avian flu outbreak removal of bird feeders and bird baths have not been required or even recommended.
H5N1 was first detected in China in 1996. Its initial impact was a very high death rate in bird populations on poultry farms. For its first 15 years, H5N1 was a seasonal infection whose occurrence was timed with the autumn migration of wild birds. In 2021, however, H5N1 changed to become a persistent, year-round infection killing millions of birds across five continents (Europe, Africa, Asia, North America and South America).
Shorebirds (willets, marbled godwits and dowitchers). Photo by I. Taylor. Wikimedia Commons
H5N1 spreads between birds via their mucous, saliva or feces. Most viral spread is from bird to bird with bird to human transmission occurring only after direct, unprotected contact with infected birds or their wastes. Human infections can result from breathing in viral ladened air droplets or dust particles, or from touching surfaces contaminated with infected bird mucous, saliva or feces and then touching eyes, mouth or nose. Appropriately used personal protective gear (masks, gloves, goggles etc.) is quite effective at blocking these routes of infection. Human illness from H5N1 ranges from a completely asymptomatic state to severe illness which occasionally has resulted in death.
Viruses can borrow and mix their genetic materials quite freely. For example, in 2020, there was an outbreak of some “low pathogenic avian influenza” (“LPAI”) in 12 turkey farms in North and South Carolina. This LPAI strain, “H7N3,” probably would not have caused serious illness in the infected birds, but to control the spread of the infection, the birds at these 12 locations were killed (or “depopulated” (to use the term utilized in the reports and papers describing the outbreak)).
Domesticated turkeys. Photo by USDA. Public Domain
Following this controlled “depopulation,” though, new outbreaks of an altered strain of H7N3 were observed in South Carolina, and the symptoms in these infected turkeys were so severe that this new strain was classified as an “HPAI.” Tracing this virus through a range of turkey farms resulted in the “depopulation” of 361,000 turkeys.
Apparently, what had occurred in these isolated populations of turkeys was the intermingling and intermixing of the genetic material from several viral strains that were simultaneously infecting the birds. The RNA from the LPAI H7N5 was shuffled together with RNA from a variety of LPAI flu strains that probably originated from wild birds. The resultant H7N3 strain was then highly pathogenic and extremely dangerous.
This same process of viral, genetic recombination occurred in a poultry population somewhere in Europe in 2021. The new strain of H5N1 which arose from this genetic re-scrambling then spread and caused the ongoing avian flu epidemic. In this European event, like in the case of the sick turkeys in the Carolinas. a population of poultry was simultaneously infected with a very common flu strain (H5N8) and several varieties of wild bird LPAI. The resultant recombination was an HPAI H5N1 with an N1 derived from wild birds. This new H5N1 was extremely contagious, persistent and virulent.
Global spread of H5N1 among wild and domesticated birds. Dark red indicates human infections, too. Wikimedia Commons
Two subtypes of this new HPAI H5N1 arose in 2021 and 2022. One spread to the coastal regions of Central Europe and was carried across the Atlantic Ocean by migrating birds. The second strain spread around the Mediterranean Sea and down into Africa. In 2022, these two H5N1 strains killed millions of birds in Europe, Africa, Asia and North and South America. The virus also began to infect a growing array of mammals including human beings!
Next week: avian flu affecting the rest of us!