possible human-to-human transmission?

What is the virus responsible for bird flu?

Avian influenza, or avian plague, is caused by infection with an RNA virus: Influenza virus type A. The subtypes of this virus are called by the abbreviations: H5N8, H5N1, H7N9, etc. The letters H and N designate hemagglutinin and neuraminidase, proteins found on the surface of the virus envelope. The different hemagglutinin and neuraminidase subtypes therefore define the influenza virus subtypes. The viruses responsible for bird flu are mainly of the H5, H7 and H9 subtypes.

Read too: Virus: Where does life begin? While this issue may seem resolved, recent work is reshuffling the cards, on viruses in particular…

How does it infect a cell?

To infect a cell, the type A Influenza virus must first attach itself to the surface of the host cell. This is where hemagglutinin comes in. It binds to sialic acid molecules present on the surface of the target cell and then allows the virus to enter the cell. The neuraminidase, thanks to its enzymatic function, allows the virus to release viral particles, called virions, that will infect other cells.

Have you ever infected humans?

At present, human-to-human transmission of the virus is still poorly documented. However, it has happened (exceptionally) that people have been infected through another animal, such as birds. To understand how this could have happened, it is necessary to look more precisely at how the virus was fixed.

As stated before, the virus binds to sialic acid. This sialic acid is linked to galactose, which is part of the carbohydrate chain of cell membrane receptors. Sialic acid and galactose can be linked by different types of glycosidic bonds, such as alpha-2,3 or alpha-2,6. Depending on its host of origin, the virus will preferentially bind to one type of receptor: alpha-2.3 or alpha-2.6.

This is where it gets interesting. Different animal species do not have the same types of receptors, which would constitute a species barrier.

For example, viruses of avian origin bind more easily to alpha-2,3 receptors on cells. Humans have alpha-2.6 receptors in their upper respiratory tract, which viruses of avian origin cannot bind. On the other hand, it has alpha-2,3 receptors in the bronchioles, pulmonary alveoli and the digestive system. This location makes contamination difficult, as it is deep in the respiratory tract, but makes the infection more serious. [1]

Possible links between sialic acid and the galactose membrane receptor in waterfowl and humans. Waterfowl have an alpha-2,3 bond between sialic acid and galactose. Humans have an alpha-2,6 bond between sialic acid and galactose in the cells of the upper respiratory tract. This difference constitutes a “species barrier”, as avian viruses – which bind to alpha-2.3 receptors – cannot bind to alpha-2.6 receptors, present in most human cells.

History of human contamination

In the literature, the first human contamination by the H5N1 virus was detected in 1997, in Hong Kong, and caused 18 cases and 6 deaths. [1]. After disappearing from the radar for 5 years, the virus reappeared in 2003, again in this territory. It was from that moment on that human infections followed one another, passing through Southeast Asia, West Asia and finally Africa, with detections in Egypt from 2006 to 2015.

An article was published in the journal The Lancet Infectious Diseases [2]compiling data identifying a total of 907 cases of human infections with the H5N1 virus from 1997 to 2015.

In pie charts, the blue section represents the proportion of non-lethal cases, in red the lethal cases and in green the unsolved cases (probable cases). The numbers indicated below the country names indicate the number of cases: lethal/non-lethal/unresolved.

While the number of 907 may seem substantial, it must be remembered that this is nothing compared to the world population and that these are cases spread over nearly twenty years! However, a question arises. How can humans be infected?

The avian influenza virus has infected many mammals

Cats, tigers, leopards, horses, guinea pigs… The avian flu virus has affected a whole group of mammals. In some cases, the hypothesis is that the animals would have been infected by eating contaminated meat.

Under what conditions can the virus be transmitted?

As mentioned earlier, alpha-2,3 receptors, targets of avian viruses, are located deep in the human respiratory system. To be contaminated, they must therefore inhale a large amount of aerosols generated by sick birds.

This contamination most often occurs in breeding grounds, farms or barns. Animal markets can also be a place of contamination but above all a place of “meeting”. [1] In fact, in these places different species are found that can potentially lead to the emergence of new viruses, through reassortment phenomena. When two viruses infect the same cell, they exchange their genetic material. This will lead to the appearance of a new virus, which has the genetic material of the two “parent” viruses. [3]

Read too: Can you catch the flu and covid-19 at the same time? What are the implications and risks of this double infection?

What are the future risks of avian flu?

The risk is therefore that a new virus subtype appears by reassortment and is therefore capable of infecting humans. For example, the pig is an animal that could potentially be an intermediate host between birds and humans because it has alpha-2.3 and alpha-2.6 receptors.[4] This means that we cannot exclude the possibility of a rearrangement between an avian and human virus in pig cells. This would give rise to a new virus, potentially capable of binding to human alpha-2.6 receptors.

The other possibility is that the pig (or other animal) serves as a “reservoir” for ancient human lineages. This means that the Influenza virus type A subtypes that previously circulated in the human population continue to circulate, but in the animal population. Later, if the infected animals re-encounter a human person, they can transmit the virus again. The Pasteur Institute takes the H1N1 subtype as an example: “ The H1N1 subtype, which causes the Spanish flu, disappeared from the human population around 1957. However, it remained present in swine, which allowed it to reappear in humans 20 years later, in 1977. “.

Breeding and marketing methods are therefore important factors in the emergence of new virus subtypes and true human-to-human transmission. Thus, rethinking our models of reproduction is necessary to avoid new global epidemics like the one of Covid-19 that hit us in 2020.

Read too: The keys to understanding the explosion of zoonoses. After Covid-19, it’s time for monkeypox to cause an epidemic. Another sign that diseases of animal origin – zoonoses – are on the rise.

Sources:

[1] Ducousso, Jerome, et al. “Avian influenza: a review of the French epizootics (2015-2017)”. Journal of Veterinary Medicinenooh 169, 2018, p. 38-51. https://hal.archives-ouvertes.fr/hal-02542811.

[2] Lai, Shengjie, et al. “Global Epidemiology of H5N1 Avian Influenza A Virus Infection in Humans, 1997-2015: A Systematic Review of Individual Case Data.” The Lancet Infectious Diseases, to fly. 16, nooh July 7, 2016, pg. e108-18. https://doi.org/10.1016/S1473-3099(16)00153-5.

[3] Vabret, A. “Emergencies and Species Barriers”. Medicine and Infectious Diseases, to fly. 34, nooh November 11, 2004, p. 506-13. https://doi.org/10.1016/j.medmal.2004.07.026.

[4] Superior Council of Public Health. Opinion on the prevention of transmission of swine and avian influenza viruses to humans. December 2021.

Ducousso, Jerome. The avian flu virus: what are the risks for humans? University of Lorraine, April 18, 2016.

Saborin, Paulina. Affinity of influenza A viruses and distribution of their receptors in different hosts, including humans: implications for species leaps. Exercise Thesis, Veterinary Medicine, National Veterinary School of Toulouse – ENVT, 2016, 113 p.

Avian Influenza — ACCES Resource Site for Teaching Life and Earth Sciences. http://acces.ens-lyon.fr/acces/thematiques/sante/epidemies-et-agents-infectieux/comprendre/grippe-aviaire.

Virology UCLOUVAIN FDP. Introduction to Virologyhttps://www.virologie-uclouvain.be/fr/chapitres/examples-selected/virus-de-la-grippe

“Will the bird flu virus be human? » Swiss Medical Magazinehttps://www.revmed.ch/revue-medicale-suisse/2007/revue-medicale-suisse-106/le-virus-de-la-grippe-aviaire-sera-t-il-human.

” Bird flu “. Pastoral Institute6 October 2015, https://www.pasteur.fr/fr/centre-medical/fiches-Maladies/grippe-aviaire.

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