Avian Influenza (AI) disease is caused by a virus that belongs to the family Orthomyxoviridae , genus Alphainfluenzavirus , this genus can also be designated as Influenzavirus type A.

Currently, the structure of Orthomyxoviruses is very well known. The genome is made up of single-stranded ribonucleic acid (RNA) molecules divided into eight segments. These segments code for the different components of the virus, with the exception of the lipid envelope, which the virus takes from the membranes of cells in the respiratory tract that it infected and where it multiplies.

It is these segmentation characteristics, added to having an RNA genome, that determines that this infectious agent has the ability to change antigenically constantly and in very short times. 

Single-stranded RNA genomes have a mutation rate approximately one million times higher than that of double-stranded DNA.

This virus has aquatic birds as its natural reservoir, among which ducks, seagulls and shorebirds are its main hosts.

Clinical manifestation and virus subtype

Due to its clinical manifestation, it is divided into highly pathogenic viruses (AP) and low pathogenic viruses (BP). 
Highly pathogenic viruses cause acute clinical disease in chickens, turkeys, and other domestic birds. This manifestation of AP has only been associated with subtypes H5 and H7.

In relation to low potogenicity viruses, they can occur as different subtypes , including subtypes H5 and H7. 

The H5 and H7 subtypes of BP can mutate to AP, which is why today, the World Health Organization asks member countries that any isolation of Avian Influenza virus subtype H5 or H7 be immediately notified, regardless of whether These are BP viruses. 

It is the manifestation of high pathogenicity that conditions a restriction in the marketing of poultry products internationally.
The clinical manifestation depends on the type of amino acid (aa) present in the cut region so that the binding site of the virus to the cellular receptor is exposed. 

The cuts are carried out by proteolytic enzymes , which act on specific substrates, therefore: 
If an amino acid is found at the cut site, it is an enzyme that performs the cut . 

While if a basic amino acid is found at the cutting site, another enzyme performs the cutting .


In 1996, a virus was isolated that has since attracted the attention of researchers. This virus was isolated from a domestic goose in the Guangdong region of China . After specific studies, this isolate was classified as lineage A/goose/. Guangdong/1/96 . 

This particular lineage lit the red light among researchers , because since its appearance it has caused the death of domestic and wild birds and people and since its isolation it has spread to more than 70 countries in Asia, Africa, Europe and America.

By 2022, the A Gs/GD lineage (A: corresponds to the Influenza type; Gs – Goose or goose; GD – Guangdong ) is already enzootic in domestic birds in at least 8 countries . Since this lineage was discovered causing disease and death in humans in Hong Kong, researchers have monitored its movement from region to region. 

Using molecular techniques it has been characterized to better understand its spread and thus help prevent its perpetuation in poultry populations. 

The results have shown the presence of specific mutations and recombination events.

This lineage has a high capacity for dissemination , therefore it has been highly studied and each group of researchers gave it a name that included the name of the isolated region, generating political crises due to its naming. 

Naming system 
Given that this lineage has a high capacity for dissemination, it gave rise to multiple forms of identification, generating confusion among research groups. For this reason, in 2007, the Working Group on the Evolution of the Gs/GD Lineage was formed, made up of three important entities : the World Organization for Animal Health (WOAH), the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), its objective was :

Develop a unified nomenclature system for the classification of HPAI viruses (H5N1) that was the isolate of origin and that gave rise to this Gs/GD lineage. Since then, 10 clades (0-9) have been identified. Of these, clade 2 is the one with the highest level of diversity, generating subclades: 

2.1 – 2.5, of these subclades 2.1 and 2.3 were realigned into 3rd order groups: 2.1.1 to 2.1.3 and 2.3.1 to 2.3.4. 
Of the latter, 2.2 and 2.3 have been the most widespread in production and wild birds.

The hemagglutinin (HA) genes of the Gs/GD lineage have diversified into multiple genetic clades, and specifically subclade has been regrouped with different neuraminidase (NA) subtypes to generate variants that circulate widely worldwide: H5N2, H5N3, H5N5, H5N6 and H5N8. 

These subtypes have spread rapidly through migratory wild waterfowl and have evolved through recombination with the predominant local low-pathogenic avian influenza viruses . 

Based on the above, the HA genes of the Gs/GD lineage that are regrouped with a different NA subtype are identified as H5Nx.


In the fall of 2014, the Eurasian clade HPAI H5N2 was identified in commercial birds in the Fraser Valley Region of southern British Columbia, Canada ; Subsequently, through samples collected from wild birds in the USA , the presence of at least three Eurasian isolates of the H5 subtype of AP was identified . For March to June 2015 , an H5N2 HPAI virus caused widespread HPAI infections in commercial poultry flocks in the Midwestern US states. 

According to the US Department of Agriculture, this virus affected a total of 49.7 million birds, its economic cost exceeded 3 billion dollars.

In December 2021, Canada reported the isolation of HPAI H5N1 in exhibition birds in the province of Newfoundland and Labrador. After this first isolation, 6 more were detected in wild birds and 4 in poultry , later in Nova Scotia. 4 outbreaks are reported in poultry farms , and on March 3, 2022, this virus was isolated again in British Columbia and Prince Edward Island.
For January 13, 2022, a case of HPAI subtype H5 is identified in the United States . This report is made from pigeon samples obtained in December 2021.

By November 4, 2022, the presence of the H5N1 subtype of Eurasian AP has been confirmed in 43 states with at least one infected flock, 594 flocks confirmed with positive isolates for said subtype, of which 254 correspond to commercial production and 340 to flocks of backyard , making a total of 49 million birds affected.

In relation to the situation in poultry farming in the US, it is important to note that contrary to what happened in 2014-2015 in this country, the behavior of isolations during 2022 has been occurring from East to West.

According to the USDA Animal and Plant Health Inspection Service (APHIS), in addition to birds, there are many species that are potentially susceptible to HPAI . 

In addition to poultry, H5N1 viruses have been detected in some mammals such as wildcat, raccoons, foxes, opossum, Amur leopard, seals, skunk, during this outbreak . This infection can cause illness, including serious illness and death in some of these cases.

Since 1995 and based on the results reported by Hernández et al., (1995) that a dose of inactivated vaccine protected birds against the challenge of a PA virus.

In 1995, the use of an emulsified vaccine against Avian Influenza was authorized , making Mexico the first country in the world to resort to the use of a commercial vaccine as a control measure; 

From 1995 to 2001, a total of 1 billion doses of inactivated emulsified vaccines were administered.
By May 1998, the use of a recombinant Pox-IA vaccine was authorized. 

From that date to December 2001, a total of 459 million doses of recombinant vaccine had been applied , 
For 2022 to date, recombinant vaccines with Newcastle vector have been developed , as well as emulsified reverse genetic vaccines.

Is it possible to neutralize the entry of infectious agents?

It is known that local immunity (Ig A) neutralizes the entry of infectious agents into the bird’s body . For this reason, if you want to neutralize respiratory infections , it is vitally important to apply vaccines at the site of infection. entry of said processes . However, in the case of Avian Influenza challenges, it is not possible for us to apply this principle , mainly:
Because the presentation of commercial vaccines does not allow it. 

On the one hand, we have vaccines with inactivated viruses whose capacity to generate localized Ig A type protection is null . 
On the other hand, in the case of recombinant vaccines , the type of application by the vector used does not lead to the generation of the type of immunity we are looking for. 
One of the main setbacks we have had in this regard is the fact that the development of current commercial vaccines does not prevent the spread of the infectious virus . There are multiple publications that have shown that the more homology there is between the HA of the vaccine and the HA of the field virus , as well as the viral concentration used to prepare the vaccines , the greater the ability to reduce the amount of virus. excreted by vaccinated and infected birds.

Something that the WOAH proposes is the possibility of vaccinating against Avian Influenza worldwide, however, vaccinating gives the possibility of the virus becoming enzootic in the different regions where isolations occur , as long as we do not have a vaccine that not only prevents disease and protect production, but also prevent its spread, we will not be able to aspire to its eradication.