Influenza Type A Viruses

duck flying over water

There are four types of influenza (flu) viruses: A, B, C and D. Wild aquatic birds, including gulls, terns, and shorebirds, and wild waterfowl, such as ducks, geese and swans are considered reservoirs (hosts) for avian influenza A viruses.

Subtypes of Influenza A Viruses

Influenza A viruses are divided into subtypes on the basis of two proteins on the surface of the virus: hemagglutinin (HA) and neuraminidase (NA). There are 18 known HA subtypes and 11 known NA subtypes. In birds, 16 HA and 9 NA subtypes have been identified. (Two additional subtypes, H17N10 and H18N11, have been identified in bats.) Many different combinations of HA and NA proteins are possible. For example, an “A(H7N2) virus” designates an influenza A virus subtype that has an HA 7 protein and an NA 2 protein. Similarly, an “A(H5N1)” virus has an HA 5 protein and an NA 1 protein.

All known subtypes of influenza A viruses can infect birds, except subtypes A(H17N10) and A(H18N11), which have only been found in bats. Only two influenza A virus subtypes A(H1N1)pdm09, and A(H3N2), are currently circulating among people. Influenza A viruses have been detected and are known to circulate in seven different animal species or groups, including humans, wild water birds, domestic poultry, swine, horses, dogs and bats. In many other animal species, avian influenza A viruses have been reported to cause occasional infections, but do not regularly spread among them (e.g., cats and seals). Equine (horse) influenza A(H3N8) virus routinely circulates and can cause illness in horses, and canine (dog) influenza A(H3N2) virus routinely circulates and can cause illness in dogs.

Lineages of Influenza A Viruses

Avian influenza A viruses that infect birds have evolved into distinct genetic lineages based on the geographic locations where they were first detected. These different lineages can be distinguished by studying the genetic make-up of these viruses. For example, avian influenza A viruses that were first detected in birds in Asia can be recognized as genetically different from avian influenza A viruses that were first detected among birds in North America. These broad lineage classifications can be further narrowed by genetic comparisons that allow researchers to group the most closely related viruses together. The host, time period and geographical location are often used in the lineage name to help further delineate one lineage from another.

Highly Pathogenic and Low Pathogenic Avian Influenza A Viruses

Avian influenza A viruses are classified into the following two categories: low pathogenicity avian influenza (LPAI) A viruses, and highly pathogenic avian influenza (HPAI) A viruses. The categories refer to molecular characteristics of a virus and the virus’ ability to cause disease and mortality in chickens in a laboratory setting pdf icon[2.55 MB, 64 Pages]external icon. HPAI and LPAI are defined and explained below:

  • Low Pathogenic Avian Influenza (LPAI):  Low pathogenic avian influenza viruses cause either no signs of disease or mild disease in chickens/poultry (such as ruffled feathers and a drop in egg production). Most avian influenza A viruses are low pathogenic and cause few signs of disease in infected wild birds. In poultry, some low-pathogenic viruses can mutate into highly pathogenic avian influenza viruses.
  • Highly Pathogenic Avian Influenza (HPAI):  Highly pathogenic avian influenza viruses cause severe disease and high mortality in infected poultry. Only some avian influenza A(H5) and A(H7) viruses are classified as HPAI A viruses, while most A(H5) and A(H7) viruses circulating among birds are LPAI A viruses. HPAI A(H5) or A(H7) virus infections can cause disease that affects multiple internal organs with mortality up to 90% to 100% in chickens, often within 48 hours. However, ducks can be infected without any signs of illness. HPAI A(H5) and A(H7) virus infections in poultry also can spill back into wild birds, resulting in further geographic spread of the virus as those birds migrate. While some wild bird species can be infected with some HPAI A(H5) or A(H7) virus subtypes without appearing sick, other HPAI A(H5) and A(H7) virus subtypes can cause severe disease and mortality in some infected wild birds as well as in infected poultry.

Both HPAI and LPAI viruses can spread rapidly through poultry flocks. HPAI and LPAI designations do not refer to or correlate with the severity of illness in cases of human infection with these viruses; both LPAI and HPAI A viruses have caused mild to severe illness in infected humans. There are genetic and antigenic differences between the influenza A virus subtypes that typically infect only birds and those that can infect birds and people.

Avian influenza A viruses rarely infect people. Five subtypes of avian influenza A viruses are known to have caused human infections (H5, H6, H7, H9, and H10 viruses). The most frequently identified subtypes of avian influenza A viruses that have caused human infections are H5, H7 and H9 viruses. Specifically, A(H5N1) and A(H7N9) viruses have caused the majority of avian influenza A virus infections reported in people, with HPAI A(H5N6) and LPAI A(H9N2) viruses also causing human infections in recent years. Human infections with other subtypes, such as A(H6N1), A(H10N3), A(H10N7), and A(H10N8), have been detected in small numbers of people. In the United States, no HPAI A(H7) virus infections have ever been reported in people; however, there have been four laboratory-confirmed cases of LPAI A(H7N2) virus infection in people. More information about avian influenza A virus infection in humans is available at Avian Influenza A Virus Infections in Humans.

Avian Influenza A(H5) Viruses

There are nine known subtypes of A(H5) viruses pdf icon[1.34 KB, 15 Pages]external icon [A(H5N1), A(H5N2), A(H5N3), A(H5N4), A(H5N5), A(H5N6), A(H5N7), A(H5N8), and A(H5N9)]. Most A(H5) viruses identified worldwide in wild birds and poultry are LPAI, but occasionally HPAI A(H5) viruses have been detected. Sporadic A(H5) virus infections of humans have occurred, such as with HPAI A(H5N1) viruses associated with poultry outbreaks in many countries. Human infections with HPAI A(H5N1) virus have been reported in 19 countries since 2003, resulting in severe pneumonia and death in more than 50% of cases. Human infections with HPAI A(H5N6) virus have been reported since 2014 from two countries with death occurring in more than 40% of cases, and human infections with HPAI A(H5N8) virus were reported from one country in 2021.

Avian Influenza A(H6) Viruses

LPAI A(H6) virus outbreaks in birds are not internationally reportable, therefore, its true prevalence is unknown. However, LPAI A(H6) viruses have been identified in various species of wild waterfowl and domestic poultry in Eurasia and the Americas.  Known subtypes of A(H6) viruses include LPAI A(H6N1) and A(H6N2). In 2013, Taiwan reported the first known human infection with LPAI A(H6N1) virus.

Avian Influenza A(H7) Viruses

There are nine known subtypes of A(H7) viruses pdf icon[1.34 KB, 15 Pages]external icon A(H7N1), A(H7N2), A(H7N3), A(H7N4), A(H7N5), A(H7N6), A(H7N7), A(H7N8), and A(H7N9)]. Most A(H7) viruses identified worldwide in wild birds and poultry are LPAI viruses. Avian influenza A(H7) virus infection of humans have occurred sporadically. The most frequently identified A(H7) viruses associated with human infections are avian influenza A(H7N9) viruses, which were first detected in China in 2013. While human infections with A(H7N9) viruses are uncommon, they have resulted in severe respiratory illness and death in approximately 40% of reported cases. In addition to A(H7N9) viruses, human infections with A(H7N2), A(H7N3), A(H7N4), and A(H7N7) viruses have been reported and have primarily caused mild to moderate illness with symptoms that included conjunctivitis and/or upper respiratory tract symptoms.

Avian Influenza A(H9) Viruses

There are nine known subtypes of A(H9) viruses pdf icon[1.34 KB, 15 Pages]external icon A(H9N1), A(H9N2), A(H9N3), A(H9N4), A(H9N5), A(H9N6), A(H9N7), A(H9N8), and A(H9N9)]; all A(H9) viruses identified worldwide in wild birds and poultry are LPAI viruses. A(H9N2) virus has been detected in bird populations in Asia, Europe, the Middle East and Africa. Sporadic avian influenza A(H9N2) virus infections have been reported in people with mild upper respiratory tract illness, although some infections have resulted in death.

Avian Influenza A(H10) Viruses

Known subtypes of A(H10) viruses include A(H10N3), A(H10N4), A(H10N5), A(H10N6), A(H10N7) and A(H10N8). A(H10N4) was found in a mink in 1984 and A(H10N5) was found in swine (pigs) in 2008. The A(H10) virus subtypes known to have caused human infections include A(H10N3), A(H10N7), and A(H10N8). Egypt reported the first human infections with A(H10N7) virus in 2004, while Australia reported human infections with A(H10N7) virus in March 2010. The first human infections with A(H10N8) virus were reported in China in December 2013. The first human A(H10N3) virus infection was reported in China in June 2021. Most A(H10) virus infections in people have resulted from exposure to infected poultry.