antigenic drift vs antigenic shift or reassortment

[Guest guest]

Deadly strain of swine flu gets under radar of the immune system

From The Times April 28, 2009 Mark , Science Editor

Flu is always a moving target for medicine because of its ability to reinvent

itself to evade the body's natural defences and vaccines and drugs.

Because the virus mutates at a high rate, the flu strains that circulate every

winter are slightly different from those of the previous year. This process,

called antigenic drift, requires the issue of fresh flu vaccines every year to

protect against the latest strains.

It does not, however, carry a pandemic threat: the genetic changes involved are

minor, so people who have already been exposed to flu generally retain a measure

of immunity. New strains created this way can spread, and sometimes kill the

young, old and infirm, but they do not sweep through entire populations.

What virologists fear is a different process, called antigenic shift or

reassortment, which has driven previous pandemics. It is this that appears to

have created the Mexican swine flu.

Antigenic shift allows flu to acquire much larger genetic changes very quickly,

creating new strains to which the human immune system is entirely naive. These

can make it much more dangerous because the body cannot immediately defend

itself.

Flu mutates this way when two different strains infect the same host at the same

time, which allows them to exchange whole sections of their genetic code.

A flu virus's genome is split into eight segments, each of which is copied

separately inside host cells, before being reassembled into daughter viruses and

released to infect other cells. When two viruses are present their segments can

get jumbled up, creating reassorted daughter viruses with genetic material from

both strains.

" That is what appears to have happened here, " said Barclay, Professor of

Influenza Virology at Imperial College, London. " From looking at the sequences,

two viruses at least have come together. "

In the case of the swine flu the original strains appear both to have been pig

viruses, which have swapped genetic material in an infected pig to create an

entirely new strain that infects humans easily. Curiously, the new virus does

not seem to cause disease in pigs. When the swine flu virus was identified as

belonging to the H1N1 family it raised hope that humans might have some residual

immunity to it, which might contain its pandemic potential. H1N1 viruses

commonly infect humans and one was included in this year's seasonal flu vaccine.

Genetic analysis, however, has now indicated that the H1N1 swine flu is too

different from human H1N1 for previous vaccinations or flu infections to offer

much protection.

" The homology [similarity] is very low, 70 per cent or less, " Professor Barclay

said. " There is very little similarity, and you would expect there to be very

little protection from antibodies to H1 human strains.

One encouraging discovery about swine flu is that analysis of its neuraminidase

protein — the N of H1N1 — indicates that it should be sensitive to the antiviral

drugs Tamiflu and Relenza, which target this protein. This bears out clinical

experience so far, which suggests that patients respond well to the drugs.

However, Professor Barclay said that viruses with N1 neuraminidase were more

likely than other strains to develop resistance to antivirals.

Lachmann, Emeritus Professor of Immunology at the University of Cambridge,

said: " Tamiflu resistance is extraordinarily widespread, and develops very

quickly. We would be very lucky if this virus does not develop resistance. "

It remains unclear why the virus has killed so many young, healthy adults — a

concern because this is characteristic of pandemic strains. One possibility is

that the virus triggers a massive immune reaction called a cytokine storm, which

is worse in fit people with a strong immune system.

This is thought to have been the chief cause of death during the Spanish Flu of

1918-19, which was caused by an H1N1 strain.

http://www.timesonline.co.uk/tol/life_and_style/health/article6182047.ece