H5N1 avian flu viruses: What's in a name?

[Guest guest]

H5N1 avian flu viruses: What's in a name?

Roos and Amy L. Becker Staff Writers

Dec 30, 2005 (CIDRAP News) – Last month, officials in Italy and

Canada aroused concern by announcing they had found an H5N1

influenza virus in wild birds. Neither country had previously been

troubled by any reports of the virulent H5N1 virus that has been

plaguing poultry and occasionally sickening and killing humans in

Asia.

But in both cases, health officials said the virus was not dangerous

and was unrelated to the H5N1 virus in Asia.

This suggested an obvious question: If a virus has the same name as

the one in Asia, why isn't it just as dangerous?

The answer has to do with the rather outdated conventions for naming

influenza viruses, according to Halvorson, a veterinary

pathologist and avian influenza expert at the University of

Minnesota in St. .

The " H " and " N " in the name of a flu virus stand for hemagglutinin

and neuraminidase, two proteins on the surface of the virus that

allow it to enter and exit host cells. Sixteen different

hemagglutinins and nine different neuraminidases have been

identified to date.

Hemagglutinin and neuraminidase were the first aspects of the flu

virus to be identified, so the nomenclature was built around the two

genes that code for them, Halvorson explained to CIDRAP News. The

types are numbered according to when they were discovered; H1 was

identified first.

However, a flu virus also has six other genes and corresponding

proteins. Thus a name like " H5N1 " is a very incomplete description

of the virus.

" The H5N1 only describes two of the eight genes, so there are six

other genes, " Halvorson said. It's possible to have an H5N1 strain

with six other genes from an avian flu virus, or an H5N1 with six

other genes from a human-adapted or pig-adapted flu virus. " That's

how far apart they can be. "

For example, the other six genes in a given H5N1 virus could be

identical to the other six genes in an H6N2 virus, he said.

In an analogy Halvorson uses with his students, he said that

assuming that all H5N1 viruses are identical would be like assuming

that all men wearing navy blazers and gray pants are the same in

other ways.

" You can have the mafia wearing that outfit or you can have a

college professor wearing that outfit—or a used car salesman, " he

said.

" We're stuck with something we have difficulty explaining because we

don't really have good nomenclature, " Halvorson summed up.

Mild viruses can turn nasty

Avian flu viruses of the H5 and H7 types can be either relatively

harmless or highly lethal to poultry—low-pathogenic or highly

pathogenic. (The conventional abbreviations are LPAI and HPAI, for

low-pathogenic and highly pathogenic avian influenza.) In fact, all

known HPAI strains are either H5 or H7 subtypes.

HPAI strains typically are detected as a result of poultry deaths,

Halvorson said. The designation of high pathogenicity generally is

based on what happens to healthy chickens when they're exposed to

the virus. If the virus kills at least 6 out of 8 chickens in a

challenge trial, it is deemed highly pathogenic.

Unfortunately, a low-pathogenic strain won't necessarily stay that

way. It can evolve unpredictably into a highly pathogenic strain—a

change that may take weeks, months, or even years.

What differentiates LP from HP strains at the molecular level,

Halvorson explained, is the nature of the hemagglutinin cleavage

site, where the hemagglutinin is split by an enzyme or some other

factor, enabling the virus to enter a host cell.

In most human and poultry flu cases, the virus is cleaved by

protease, an enzyme found in the respiratory tract, Halvorson said.

But an HPAI virus doesn't need that protease assistance to

split; " It gets cleaved almost by itself. " Consequently such viruses

can spread in many tissues, not just the respiratory tract.

Scientists now can identify HPAI viruses not only by how they affect

chickens, but also by examining the amino acid sequences at the

hemagglutinin cleavage site, according to Halvorson. (Most of the

time, however, HPAI viruses are detected by their effects on

poultry.)

Generally, HPAI viruses are defined by having four basic (as opposed

to acidic) amino acids at the cleavage site, he said. However, in

the last few years there were two cases in which an HPAI virus

emerged without those four basic amino acids. Those viruses had an

insert from another gene at the cleavage site that allowed it to

split more easily. The outbreaks involved H7 strains in Chile in

2002 and in British Columbia in 2004.

Viral instability tough on poultry industry

Those outbreaks illustrated once again the highly unstable nature of

flu viruses. Mutations occur constantly as the virus tries " to find

the best fit for the species " it depends on, Halvorson said.

Flu viruses, including H5 and H7 varieties, circulate all the time

in wild waterfowl, usually without making them sick. " Occasionally

there's going to be spillover into poultry someplace. Even though it

may be low-path, it's cause for concern, " he explained.

The US poultry industry is " 99.99% free of influenza, " but every

year flu turns up in one or more flocks in one or several states, he

added.

When the strain is a low-pathogenic H5 or H7, there's no way to

predict if, or how soon, it might evolve into a highly pathogenic

form. In the outbreaks in Chile and British Columbia, the transition

took just a few weeks. But in Pennsylvania in 1983, it took 6

months. And a low-pathogenic H7N2 virus has persisted in live-bird

markets in New York since 1994 without changing into the lethal

form.

The World Organization for Animal Health (OIE) recently recommended

that all low-pathogenic H5 and H7 avian flu outbreaks be reported to

veterinary authorities, given the risk that they can turn virulent,

Halvorson said. This has increased the level of awareness and

concern about the viruses.

" So states like Minnesota, which never destroyed any poultry before,

if we were to get an H5 or an H7 [that's low-pathogenic], we'd be

under tremendous pressure to destroy the flock, " he noted.

The heightened concern has economic consequences. Halvorson said

there's no legal basis for banning poultry imports from an area

where LPAI has been found, yet the US Department of Agriculture

promptly (though temporarily) banned poultry from British Columbia

recently when an LPAI strain turned up there.

H5N1 may lead to use of risky vaccines

As the virulent H5N1 virus continues to evolve and kill poultry in

Eurasia, Halvorson predicted, scientists may turn toward a hitherto

unthinkable option: a live influenza vaccine for poultry. Such

vaccines use a live but weakened form of flu virus.

Such vaccines have long been considered too risky in

poultry. " Because these viruses are so unstable, the concern was

that they could recombine with some other virus that's there and

make something worse, " he said.

But with the H5N1 virus now present in 15 or more countries and

endemic in several of them, using a live vaccine may be worth the

risk, he said. " People are now saying we've got to attack this with

everything at our disposal, and that'll have to include a live

vaccine. The door is open now for a live H5 vaccine in birds. "

Live vaccines offer important advantages, Halvorson explained. One

is that they require less antigen (active ingredient) than killed

vaccine. A live vaccine may contain too few copies of the weakened

virus to trigger an immediate immune response, but once inside the

host, the virus replicates to the point where the immune system

detects and responds to it. A killed virus must be injected in

larger doses, because it doesn't multiply inside the recipient.

A second advantage is that live viruses don't have to be injected

into each bird individually; they can be put into drinking water or

sprayed into the air in a chicken coop. That way, hundreds or

thousands of birds can be immunized quickly. Killed viruses, by

contrast, must be injected, because there's no other way to

administer them that will bring them into contact with the immune

system.

Earlier this week, not long after Halvorson predicted that live

vaccines would be used against H5N1, Chinese veterinary officials

announced they had developed a live-virus vaccine covering both H5N1

flu and another devastating poultry virus, Newcastle disease.

In a follow-up interview, Halvorson said it appeared that the

Chinese vaccine involved a genetically engineered Newcastle disease

virus, rather than a live influenza virus. " I believe they're

talking about a recombinant Newcastle vaccine virus that will

express a protein from an [H5N1] influenza virus, and the body would

produce antibodies against that H5 virus, " he said.

" A similar thing was done here [in the United States] a few years

ago, " but it didn't lead to a marketable vaccine, he said.

See also:

Nov 11 CIDRAP News story dealing with H5N1 virus in Italy

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/nov1

105avian.html

Nov 21 CIDRAP News story mentioning H5N1 virus found in Canada

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/nov2

105canada.html