Bird Flu - Haemagglutinin

Crossing the Species Barrier

Most emerging infectious diseases (EID) in humans, either newly recognised ones or those with new geographical or population dynamics, originate from animal reservoirs. Though the transfer of viruses between different host species is rare, those that do cross the species barrier often lead to severe outbreaks; further adaptation can then result in the emergence of variants worldwide. For a virus to cross between species, several genetic adaptations need to occur in the virus. In general, there are three specific barriers a virus needs to cross in order to become established in a new host species:

(1) Cross-species host-host interactions

Interaction between the infected host species (e.g. bird) and the recipient species (e.g. human) is the first step in enabling the virus to be transferred to a new host - for example, the handling of infected waterfowl, where the infection can be transferred through saliva, nasal secretions and faeces. The increase in travel and trade, farming practices, and the expansion of both human and farm populations, have removed many of the barriers that limit contact between species, especially with regards to AIV.

(2) Virus-host interactions

Interaction between the virus and the new host affect the ability of the virus to establish an infection and to replicate. These barriers involve the recipient host’s defence system (e.g. mucus, macrophages) that can prevent the virus from establishing itself, as well as the specificity of receptor molecules found on host cell membranes that govern whether a virus can enter and infect a cell. In addition, once the virus has infected a cell, it must be able to take over the host cell’s machinery in order to replicate and be released successfully, so as to spread the infection. Other concerns for the virus involve avoiding the host innate immune response (e.g. interferons), being able to travel via the lymphatic or blood systems to spread to other tissues, and finally, its ability to be shed from its current host in order to infect others.

(3) Intraspecies host-host interactions

The final barrier to be overcome is the transfer of the virus between infected and non-infected hosts within the new species. This depends upon the number of susceptible individuals (if there is any immunity within a population), the biological characteristics and evolutionary potential of the virus, and environmental conditions that may aid the transfer of the virus. Viral characteristics such as its level of infectivity, the length of infectious period within an individual, and the length of the transmission period before symptoms become visible all play a critical role.

Recent Influenza A Virus Pandemics

Influenza viruses have most likely been the cause of periodic epidemics for thousands of years, with reports of influenza-like diseases since the Middle Ages, although it is only since the mid-19^th century that we have been able to collect details of the viral strains involved. Some of the recorded outbreaks in humans have been:

· H3N8 emerged in 1889 to cause an epidemic.

· H2N8 emerged in 1900 to cause an epidemic.

· H1N1 emerged in 1918 to cause the Spanish Influenza pandemic (although it most likely started in the United States), which had the highest death toll of any influenza pandemic in the 20^th century (killing 20-40 million people worldwide). This remained the major epidemic strain until 1957; H1N1 was then re-introduced in 1977, when it was called Russian Influenza, and still persists today.

· H2N2 is an Asian subtype that emerged in the 1957 pandemic as an avian-to-human-adapted virus. This strain lasted until the 1960s.

· H3N2 is a Hong Kong subtype that emerged in Asia in the 1968 pandemic as an avian-to-human-adapted virus. This strain continues today.

· H5N1 is a highly pathogenic Asian strain that emerged as a pandemic in birds in 2003/4 (though it was first detected in geese in China in 1996), and which is capable of causing severe illness in humans through direct contact with infected birds. It has been commonly called Bird Flu, and has resulted in the culling of hundreds of millions of birds in an attempt to control its spread. There is no evidence that H5N1 can be spread by human-to-human contact, but its possible adaptation poses a potential human pandemic threat for which vaccines are being prepared.

Current influenza A strains causing human disease tend to be H1N1, H3N2, and the more recent H1N2. Repeated infection with the same viral subtype occurs because of antigenic changes in the HA and NA surface glycoproteins that occur through genetic mutation, thereby enabling the virus to spread amongst populations immune to earlier variants. In addition, new subtypes can arise from genetic reassortment between two different strains, as occurred between H1N1 and H3N2 to produce the recently introduced H1N2 strain.

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