Anniversary

A year ago, few realized the significance of a report from a remote area in China. I didn’t. Many of us still don’t, but I think we should.

"Prior to the ongoing H5N1 epizootic [the animal equivalent of an epidemic], HPAI [High Pathogenic Avian Influenza] had only once affected wild birds significantly. This outbreak occurred in South Africa in 1961 and caused the death of approximately 1300 common terns. (Becker, 1966)[1] It appeared that HPAI was a disease of domesticated birds and that wild birds usually only harbored the low-pathogenic form of these viruses.”

(Capua & Alexander, 2006)[2] 

A very significant outbreak

This changed dramatically in April and May 2005, when many thousands of wild aquatic birds, including gulls, cormorants, ducks, and mostly bar-headed geese, were found dead in a nature reservation at Qinghai Lake in China. The cause of death was a new strain of the avian influenza Type A H5N1 virus. (Liu et al., 2005)[3]

Most waterfowl coexist peacefully with avian influenza viruses and are resistant to H5N1. What made the difference at Qinghai Lake?

A key mutation in H5N1

Tests with lab chickens and mice showed this strain of H5N1 to be much more deadly than the usual H5N1, suggesting that it could be a threat to other mammals, which soon turned out to be true. One of the characteristics seen in the viruses that were isolated from the dead birds was a mutation in the PB2 gene. This variation, E627K, caused the replacement of just one amino acid with another in the gene’s protein product, a change that makes the H5N1 virus more deadly.

What makes E627K dangerous?

Human influenza viruses do not spread in birds, and bird influenza viruses generally do not cause disease in humans. (Beare & Webster, 1991)[4] One reason is that typical bird flu viruses need temperatures of about 40 – 41 degrees Celsius to replicate. These temperatures are normal in bird intestines, the typical site of infection in birds. Human influenza viruses are adapted to a lower temperature range, down around 33 degrees Celsius, which is typical for the human upper respiratory tract. The PB2 gene contains instructions for making copies of the virus, and the instruction located at the 627 th  amino acid helps determine at which temperatures this replication functions best. (Massin et al, 2001)[5] 

The E627K version of PB2 is found in human H1, H2, and H3 flu virus strains where it supports faster replication at low temperatures. After Qinghai, the E627K mutation shows up regularly in the H5N1 bird flu strain that has migrated with wild birds westward to Europe and Africa. When mammals get infected with this strain, the disease is more serious than with H5N1 infections that do not have the E627K mutation.

A marker for migration

Since E627K had not previously been observed in H5N1 virus sub-types, it can serve as a marker for tracking the spread of the virus strain from Qinghai Lake. In summer and fall of 2005, a succession of H5N1 outbreaks was moving westward to Mongolia, Kazakhstan, and Siberia, specifically Chany Lake reserve near Novosibirsk. In fall 2005, outbreaks were reported in Romania, Croatia, the Crimea, Turkey, and on to Africa. All were traceable to Qinghai.

H5N1 returns to Qinghai

If there were any doubts that H5N1 was spread by migrating birds, they should be diminished quite a bit, as this week news comes from Qinghai that after a year, the virus has returned.[6] Genetic analysis will reveal whether E627K has returned as well. If so, the E627K strain of H5N1 will likely mix with other strains and spread from Qinghai along more bird migration routes. We are not released from watchful waiting yet.

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[1] Becker WB.

The isolation and classification of tern virus: influenza virus A/tern/South Africa/1961.

Journal of Hygiene, 1966; 64:309-320.

[2] Capua I, Alexander DJ.

The challenge of avian influenza to the veterinary community.

Avian Pathology 2006;35(3):1_/17. Preview.

Cit: Avian Influenza - Worldwide (108): Denmark, Germany; http://www.promedmail.org.

[3] Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang XW, Zhang XL, et al.

Highly pathogenic H5N1 influenza virus infection in migratory birds.

Science. 2005 Aug 19;309(5738):1206. Epub 2005 Jul 6.

[4] Beare AS, Webster RG.

Replication of avian influenza viruses in humans.

Arch Virol. 1991;119(1-2):37-42.

[5] Massin P, van der Werf S, Naffakh N.

Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses.

J Virol. 2001 Jun;75(11):5398-404.

[6] http://today.reuters.co.uk/news/newsArticle.aspx?type=worldNews&storyID=2006-05-05T093311Z_01_PEK211314_RTRUKOC_0_UK-BIRDFLU-CHINA.xml&archived=False

Comments

[lynn]

Right now, at this time, how much longer until it becomes an epidemic throughout? What are we going to do? Will we have a vaccine for this?