The first known strain of HPAI A(H5N1) (called A/chicken/Scotland/59) killed two
flocks of chickens in Scotland in 1959; but that strain was very different from
the current highly pathogenic strain of H5N1. The dominant strain of HPAI
A(H5N1) in 2004 evolved from 1999 to 2002 creating the Z genotype. It has also
been called "Asian lineage HPAI A(H5N1)".
Asian lineage HPAI A(H5N1) is divided
into two antigenic clades. "Clade 1 includes human and bird isolates from
Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade
2 viruses were first identified in bird isolates
from China, Indonesia, Japan, and South Korea before spreading westward to the
Middle East, Europe, and Africa. The clade 2 viruses have been primarily
responsible for human H5N1 infections that have occurred during late
2005 and 2006, according to WHO. Genetic analysis has identified six subclades
of clade 2, three of which have a distinct geographic distribution and have
been implicated in human infections.
·
Subclade
1, Indonesia
·
Subclade
2, Europe, Middle East, and Africa (called EMA)
·
Subclade
3, China"
A 2007 study focused on the EMA
subclade has shed further light on the EMA mutations. "The 36 new isolates
reported here greatly expand the amount of whole-genome sequence data available
from recent avian influenza (H5N1) isolates. Before our project,
GenBank contained only 5 other complete genomes from Europe for the 2004–2006
period, and it contained no whole genomes from the Middle East or northern
Africa. Our analysis showed several new findings. First, all European, Middle
Eastern, and African samples fall into a clade that is distinct from other
contemporary Asian clades, all of which share common ancestry with the original
1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show
a consistent picture of 3 lineages, as illustrated by the HA tree shown in
Figure 1. Two of the clades contain exclusively Vietnamese isolates; the
smaller of these, with 5 isolates, we label V1; the larger clade, with 9
isolates, is V2. The remaining 22 isolates all fall into a third, clearly
distinct clade, labeled EMA, which comprises samples from Europe, the Middle
East, and Africa. Trees for the other 7 segments display a similar topology,
with clades V1, V2, and EMA clearly separated in each case. Analyses of all
available complete influenza (H5N1) genomes and of 589 HA sequences placed the
EMA clade as distinct from the major clades circulating in People's Republic of
China, Indonesia, and Southeast Asia."
Terminology
H5N1 isolates are identified like this
actual HPAI A(H5N1) example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1):
·
A stands for the species of influenza
(A, B or C).
·
chicken is the species the
isolate was found in
·
CU-K2 identifies it from other influenza
viruses isolated at the same place
·
04 represents the year 2004
·
H5 stands for the fifth of several known
types of the protein hemagglutinin.
·
N1 stands for the first of several known
types of the protein neuraminidase.
Other examples include: A/duck/Hong
Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and
A/shoveler/Egypt/03(H5N2).
As with other avian flu viruses, H5N1
has strains called "highly pathogenic" (HP) and
"low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent,
and mortality rates in infected flocks often approach 100%. LPAI viruses have
negligible virulence, but these viruses can serve as progenitors to HPAI
viruses. The current strain of H5N1 responsible for the deaths of birds across
the world is an HPAI strain; all other current strains of H5N1, including a
North American strain that causes no disease at all in any species, are LPAI
strains. All HPAI strains identified to date have involved H5 and H7 subtypes.
The distinction concerns pathogenicity in poultry, not humans. Normally a
highly pathogenic avian virus is not highly pathogenic to either humans or
non-poultry birds. This current deadly strain of H5N1 is unusual in being deadly to so many
species, including some, like domestic cats, never previously susceptible to
any influenza virus.
Genetic structure and related subtypes
H5N1 is a subtype of the species
''Influenza A virus'' of the ''Influenzavirus A'' genus of the
''Orthomyxoviridae'' family. Like all other influenza A subtypes, the H5N1
subtype is an RNA virus. It has a segmented genome of eight
negative sense, single-strands of RNA, abbreviated as PB2, PB1, PA, HA, NP, NA,
MP and NS.
HA codes for hemagglutinin, an
antigenic glycoprotein found on the surface of the influenza viruses and is
responsible for binding the virus to the cell that is being infected. NA
codes for neuraminidase, an antigenic glycosylated enzyme found on the surface
of the influenza viruses. It facilitates the release of progeny
viruses from infected cells.
The hemagglutinin (HA) and
neuraminidase (NA) RNA strands specify the structure of proteins that are most
medically relevant as targets for antiviral drugs and antibodies. HA and NA are also used as the
basis for the naming of the different subtypes of influenza A viruses. This is
where the ''H'' and ''N'' come from in ''H5N1''.
Influenza A viruses are significant for
their potential for disease and death in humans and other animals. Influenza A
virus subtypes that have been confirmed in humans, in order of the number of
known human pandemic deaths that they have caused, include:
·
H1N1,
which caused the 1918 flu pandemic ("Spanish flu") and currently is
causing seasonal human flu and the 2009 flu pandemic ("swine flu")
·
H2N2,
which caused "Asian flu"
·
H3N2,
which caused "Hong Kong flu" and currently causes seasonal human flu
·
H5N1,
("bird flu"),
which is noted for having a strain (Asian-linage HPAI H5N1)
that kills over half the humans it infects, infecting and killing species that
were never known to suffer from influenza viruses before (e.g. cats), being
unable to be stopped by culling all involved poultry - some think due to being
endemic in wild birds, and causing billions of dollars to be spent in flu
pandemic preparation and preventiveness
·
H7N7,
which has unusual zoonotic potential and killed one person
·
H1N2,
which is currently endemic in humans and pigs and causes seasonal human flu
·
H9N2,
which has infected three people
·
H7N2,
which has infected two people
·
H7N3,
which has infected two people
·
H10N7,
which has infected two people
Low pathogenic H5N1
Low pathogenic avian influenza H5N1 (LPAI H5N1) also called "North
American" H5N1 commonly occurs in wild birds. In most cases, it causes
minor sickness or no noticeable signs of disease in birds. It is not known to
affect humans at all. The only concern about it is that it is possible for it
to be transmitted to poultry and in poultry mutate into a highly pathogenic
strain.
·
1975
– LPAI H5N1 was detected in a wild mallard duck and a wild blue goose in
Wisconsin.
·
1981
and 1985 – LPAI H5N1
was detected in ducks by the University of Minnesota conducting a sampling
procedure in which sentinel ducks were monitored in cages placed in the wild
for a short period of time.
·
1983
– LPAI H5N1 was detected in ring-billed gulls in Pennsylvania.
·
1986
- LPAI H5N1 was detected in a wild mallard duck in Ohio.
·
2005
- LPAI H5N1 was detected in ducks in Manitoba, Canada.
·
2008
- LPAI H5N1 was detected in ducks in New Zealand.
·
2009
- LPAI H5N1
was detected in commercial poultry in British Columbia.
"In the past, there was no
requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so
states and universities tested wild bird samples independently of USDA. Because
of this, the above list of previous detections might not be all inclusive of
past LPAI H5N1 detections. However, the World Organization for Animal Health
(OIE) recently changed its requirement of reporting detections of avian
influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be
reported to the OIE because of their potential to mutate into highly pathogenic
strains. Therefore, USDA now tracks these detections in wild birds, backyard
flocks, commercial flocks and live bird markets."
High mutation rate
Influenza viruses have a relatively high mutation rate
that is characteristic of RNA viruses. The segmentation of its genome
facilitates genetic recombination by segment reassortment in hosts infected
with two different influenza viruses at the same time. This doesn't mean that
one amino acid substitution can cause a pandemic, but it does mean that one
amino acid substitution can cause an avian flu virus that is not pathogenic in
humans to become pathogenic in humans.
Influenza A virus subtype H3N2 is
endemic in pigs in China, and has been detected in pigs in Vietnam, increasing
fears of the emergence of new variant strains. The dominant strain of annual
flu virus in January 2006 was H3N2, which is now resistant to the standard
antiviral drugs amantadine and rimantadine. The possibility of H5N1 and H3N2
exchanging genes through reassortment is a major concern.
If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could
shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of
H3N2.
Both the H2N2 and H3N2 pandemic strains contained avian influenza virus RNA segments. "While the pandemic
human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through
reassortment between human and avian viruses, the influenza virus causing the
'Spanish flu' in 1918 appears to be entirely derived from an avian
source".
Sumber : http://www.news-medical.net/
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