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Meet the virus behind the Swine flu scare
Dr Caroline Knox
Originating in Mexico where it has caused several
deaths in the last week, the illness has spread worldwide and, at the time of
writing this article, confirmed cases have been reported in the USA, Europe, the
Middle East, Japan, New Zealand and Australia. This week the World health
Organisation raised its level of risk for an influenza pandemic (continental or
worldwide spread of an infectious disease) to phase 5, indicating significant
human-human transmission and likelihood of a full-blown pandemic.
This scenario has not been seen since 1968 and is alarming governments,
health professionals and scientists alike, not to mention the general public. So
what is ‘the swine flu’ and what is the nature of the causative agent? Swine
influenza or “swine flu” is a highly contagious respiratory disease of pigs
spread by aerosols and characterised by high fever, lethargy, lack of appetite,
respiratory infection and, in severe cases, diarrhoea and vomiting. Outbreaks
occur annually in pig populations leading to high morbidity, and a mortality
estimated at between 1-4%. In many countries, vaccination is routine as a
preventative measure against an illness which results in significant economic
losses to their agricultural industries.
California Dept of Health Services |
The culprit is swine influenza virus A, subtype H1N1. Like all influenza
viruses, it contains RNA as genetic material enclosed in a lipid envelope
derived from the host cell plasma membrane during budding. The viral envelope is
studded with two glycoproteins namely, hemaglutinin (HA) and neuraminidase (NA)
which are essential for infection of host cells and also for the release of
newly generated virus particles that go on to infect neighbouring cells. Like
all viruses, swine influenza viruses are obligate intracellular parasites that
are entirely dependent on the host cell for propagation, and hijack cellular
transcriptional and translational machinery to complete their lifecycle. Swine
influenza viruses or SIVs do not normally infect humans although they have been
known to do so in the past and people who work with pigs are at risk of
infection.
Types of influenza viruses
Three major classes of influenza viruses are currently recognised: A, B and
C. Types B and C infect humans only, the former causing annual epidemics and the
latter not considered clinically important. Class A viruses, by contrast, have a
broad host range infecting birds, humans, pigs, horses, dogs, seals, whales and
even large cat species. There are 16 known HA proteins and 9 known NA proteins
which can be present in various combinations creating many antigenically
different subtypes of class A viruses eg. H1N1, H3N2, H16N3, H7N2 as so on.
Within each subtype there are many different strains, and some of these
strains are specific for particular animal species and will not normally infect
another. Only three influenza virus A subtypes are known to infect humans and
four are endemic in pigs: human and swine H1N1 strains currently causes annual
epidemics in both humans and pigs respectively.
It is important to emphasise that influenza viruses tend to be species
specific even if they are of the same subtype or strain. For example, avian
viruses do not normally infect humans or other animals simply because the
receptor proteins that are required for them to enter cells and replicate are
either not present or are poorly accessible.
Likewise, the H1N1 swine strain does not usually infect and cause illness in
humans: a different “human” H1N1 strain is involved. Having said this, certain
influenza viruses have managed to cross the species barrier and cause disease in
other animals. The notorious, highly pathogenic H5N1 avian influenza virus
caused alarm a couple of years ago when it was transmitted to poultry
populations probably by wild birds, and from there to humans causing many deaths
and the slaughter of millions of poultry.
A second example is the current H1N1 strain, a swine influenza virus that has
managed to jump from pigs to humans. Unlike H5N1 which is still around but has
not gained the capacity to spread easily between people, H1N1 is different. In
the last week, significant human to human transmission has already occurred
threatening yet another influenza pandemic which, according to scientists, is
long overdue. Three serious influenza pandemics occurred in the 20th century:
the 1918 “Spanish flu” responsible for more than 40 million deaths, followed by
the 1957 “Asian” and 1968 “Hong Kong flu” which killed between 1 and 3 million
people worldwide.
Antigenic shift
Given that viruses are generally species-specific, the question arises as to
how a virus that is endemic in pigs is now causing serious disease in humans.
Influenza viruses (and RNA viruses in general) are extremely changeable and new
strains are continually emerging. There are two major reasons for this. First
they possess genetic material composed of RNA rather than DNA, and the viral
enzymes that replicate the RNA are notoriously error prone, making small
mistakes or mutations while copying the viral genes. This process results in
viral variant strains that differ genetically from the original parental virus
and is referred to as antigenic drift. If such mutations occur in the genes
encoding HA and/or NA, the protein may have a slightly altered configuration
that is not recognised so well by circulating antibodies, thus rendering
vaccines based on the original strain of the virus less effective. Secondly,
because influenza viruses carry their genes on eight separate segments, a more
sinister event known as “antigenic shift” can occur upon infection.
The way this works is that if an animal is simultaneously infected with two
or more different influenza viruses, say one that is an avian virus and the
other a human virus, the two viruses can exchange or “reassort” their genes
producing a hybrid variant carrying both human and bird genetic material. This
novel virus may carry HA or NA proteins that are antigenically very different
from the original parental strains, and if capable of infecting humans, would
cause disease and possibly death because the immune system has not been exposed
to it before and is unable to eliminate it. Pigs are important “mixing vessels”
in which these reassortant viruses arise because they possess the receptors that
are required for infection by both human (α2,6) and avian (α2,3) influenza
viruses.
This is exactly what has happened in Mexico. Pigs have by chance become
infected with a combination of avian, human and swine H1N1 strains of influenza
virus. Reassortment has resulted in a brand new H1N1 strain carrying genetic
material of bird, human and pig origin, and retaining the ability to infect
humans. Probably because of intensive farming practices where animals are housed
together in crowded conditions, and also its contagious nature, the new virus
strain very quickly spread amongst the pigs, infected farm workers in close
association with the animals and from there spread to the community and beyond.
It is still unclear why the novel strain has been so deadly in Mexico but not in
other countries where it has been reported. It has been suggested that symptoms
have been made worse by other circulating viruses or that isolation and
treatment of infected people took place at a later stage than elsewhere.
Preventing infections
So what can we do to control this new influenza outbreak? We can try and
prevent the illness from spreading primarily by avoiding all non-essential
travel to places where cases have been confirmed. If this is not possible then
observing good hygiene practices such as frequent hand washing can help prevent
infection: viruses generally do not survive very long outside of their hosts,
but it is now known that influenza particles can reside on hard surfaces such as
steel for over 24 hours and still be infectious. Since the illness is spread by
coughing and sneezing (and NOT by eating properly cooked pork), avoiding crowded
places and close contact with people who have influenza-like symptoms is also
wise.
Fortunately the novel H1N1 virus has so far proved sensitive to the drug
Tamiflu which developed countries have stockpiled in preparation for a scenario
like this. Tamiflu is a NA inhibitor: it prevents the action of neuraminidase in
releasing new virus particles from infected cells, thereby reducing the spread
of the virus and lessening the symptoms of influenza.
In many countries “flu” vaccines are available to prevent illness and these
are manufactured based on strains of the virus that are predicted to circulate
in the next influenza season. It is not certain whether the currently available
vaccine would be effective against this novel H1N1 strain because it is
genetically different to strains that were used to prepare it. Scientists are
currently working on a vaccine using H1N1 virus that has been isolated from
infected patients in Mexico and the US.
We still do not know very much about the nature of this new influenza virus
strain, how efficient it is in transmitting itself from human to human, how
virulent it will prove to be and how far it will spread. But in the 21st century
we are far better prepared for the emergence of pandemic influenza in terms of
higher standards of healthcare, a better understanding of the biology and
epidemiology of the pathogen and improved methods of diagnosis and treatment for
the illness. However, we must never underestimate the potential of influenza
virus and other pathogens to pose a massive threat to human and animal health
and also to the global economy. Scientists in Africa and in the rest of the
world have an ever increasing and vital role to play in this exciting and
exploding field of research.
More information:
 Dr
Caroline Knox is a virologist based at Rhodes University in the Department of
Biochemistry, Microbiology and Biotechnology.
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