When you read or listen to news about the bird flu, you might hear about the spread of H5N1, the mad dash to buy Tamiflu, or the warnings of a pandemic. However, one thing that is overlooked often is the virus's mechanics. In other words, how does it work?
Anatomy of a virus
Diagram of an influenza virus (Paul Digard)
If you were to look at an influenza virus through a microscope, it would look like a sphere with many spikes and mushroom shaped objects on its surface. The exterior of the virus is composed of a lipid (fat) envelope covered with two types of protein molecules called surface antigens. The spikes are known as hemagglutinin (HA) and the mushrooms are known as neuraminidase (NA). Each hemagglutinin spike is made up of three entwined molecules while each neuraminidase mushroom is comprised of four entwined molecules. Also on the surface of the virus are M2 proteins, which allow the virus to adjust its interior acidity. Inside the lipid envelope, there are eight RNA gene segments called RNPs (RNA molecule+ Nucleoprotein+ Polymerases). Finally, there are the ball shaped M1 proteins, which act as cushions for the RNPs inside.
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A CLOSER LOOK: What's in a name?
H5N1, H1N1, H3N2... the flu virus designations are interesting and puzzling. But how do scientists come up with these strange names. According to experts, there are 15 different types of hemagglutinin molecules and 9 different types of neuraminidase molecules. Virologists identify Influenza A viruses by their specific hemagglutinin and neuraminidase molecules. In 1980, scientists adopted a general formula for naming Influenza A viruses, HxNy (x represents the type of hemagglutinin molecule and y represents the type of neuraminidase molecule.)
For example, an avian flu virus with hemagglutinin molecule 3 and neuraminidase molecule 2, its name would be H3N2.
How influenza replicates
The process of cell replication can be explained in three phases: initiation, replication, and release.
Initiation
During initiation, the hemagglutinin (HA) spikes bind to the surface of a cell. After binding, the virus is enveloped by a capsule made from the cell's membrane, which then breaks off from the surface and goes into the cell. This process is known as endocytosis. After entering the cell, the virus's M2 protein pumps ions into the capsule, to make it more acidic. When the capsule becomes acidic enough, the virus will merge with the capsule. Eventually, a hole is formed and the RNPs leave the capsule, heading straight for the cell's nucleus, where replication begins.
Diagram of influenza replication (Microbiology @ Leicaster)
Replication
The RNPs enter the nucleus, where new viral RNA and proteins will be produced. Inside the nucleus, the virus's genetic blueprint (known as vRNA) produces messenger RNA (mRNA) and direct copies of its genetic material (cRNA). The mRNA 'oversees' the making of various proteins, while the cRNA is used to make additional copies of the virus's genetic material. Hemagglutinin, neuraminidase, and M1 proteins form on the outside of the cell membrane, while newly made nucleoproteins combine with vRNA to form nucleocapsids, another name for the RNPs. With everything in place, the release phase begins.
Release
During the final phase, the nucleocapsids are assembled and the new virus particles begin to take shape. After assembly, the viruses are released from the cell, in a process known as budding. New virus particles are gradually released from the cell for several hours until the cell eventually dies off. The new viruses then attach themselves to new cells, starting the process of replication again.
Three essential facts
1. RNA is extremely error prone: on average, each new virus differs from its parent by at least one nucleotide.
2. Influenza is the only virus that undergoes true antigenic drift (genetic changes in the virus that occur because of errors in replication.)
3. Two different viruses can infect a cell at the same time. For instance, if human and an avian flu virus infect a pig cell, they can swap genes. This swap results in a new flu subtype that has both avian and human flu characteristics. This 'reassortment' is known as antigenic shift.
WHAT DO YOU KNOW ABOUT “A” FLU (SWINE FLU)
1. You would have heard that swine flu is a pandemic, but what does this word mean?
2. Is it the same disease as the normal (seasonal flu)?
3. Has it got any relationship with avian flu (bird flu)?
4. Tell wether these sentences are true or false
a. We’ve got a vaccine for “A” flu but it is not very effective.
b. “A” flu is more dangerous than seasonal flu because it’s mortality rate is bigger.
c. A mask for your mouth and nose is a good means not to catch flu.
d. The best means to prevent catching “A” flu is to clean frequently your hands.
e. Young people catch “A” flu more easily than seasonal flu.
f. Symptoms of “A” flu are more serious than those of the seasonal flu.
g. The use of antibiotics is very effective for treating the flu.
h. We have not at present any good treatment for “A” flu.
i. Normal vaccine for seasonal flu is also useful for “A” flu.
j. The flu is caused by a Virus.
k. But “A” flu is caused by a bacteria.
l. Normal antivirals are not effective against “A” flu
m. Risk goups are the same as with seasonal flu.
5. What`s “Tamiflu”?
6. Describe very shortly what a virus is. If possible draw a picture.
7. Have you ever heard about the “Spanish flu”?. If not look for information.
8. The “World Health Organisation” (WHO) don´t consider any more the term “swine flu”as correct, instead they propose the term “H1N1 flu”. Could you give a reason for that?
Pandemic (H1N1) 2009 - update 67
Weekly update
As of 20 September 2009, there have been more than 300,000 laboratory confirmed cases of pandemic influenza H1N1, 3917 deaths, in 191 countries and territories reported to WHO.
As more and more countries have stopped counting individual cases, particularly of milder illness, the case count is significantly lower than the actually number of cases that have occurred. While the case counts no longer reflect actual disease activity, WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.
In the temperate regions of the northern hemisphere, influenza-like-illness (ILI) activity continues to increase in many areas. In North America, the United States has reported continued increases in activity above the seasonal baseline for the last 2 to 3 weeks, primarily in the southeast but now also appearing in the upper midwest and the northeast. In Europe and Central and Western Asia, the United Kingdom is reporting regional increases in ILI activity in Northern Ireland and Scotland and the Netherlands, France, Ireland, and Israel are reporting rates above the seasonal baseline. In In Japan, influenza activity continues to be slightly above the seasonal epidemic threshold. The increases in ILI activity have been accompanied by increases in laboratory isolations of pandemic influenza H1N1 2009 in most of these areas.
In the tropical regions of the Americas and Asia, influenza activity remains variable. In parts of India, Bangladesh and Cambodia, influenza transmission continues to be active, while other countries in the Southeast Asia have been recently reporting declining transmission (Indonesia, Singapore and Thailand). Although most countries in the tropical regions of the Americas are still reporting regional to widespread geographic spread of influenza activity, there is no consistent pattern in the trend of respiratory diseases. Peru and Mexico have reported an increasing trend in some areas, while most others are reporting an unchanged or decreasing trend (most notably Bolivia, Venezuela and Brazil).
In the temperate regions of the southern hemisphere, influenza transmission has largely returned to baseline (Chile, Argentina, and New Zealand) or is continuing to decline (Australia and South Africa).
All pandemic H1N1 2009 influenza viruses analyzed to date have been antigenically and genetically similar to A/California/7/2009-like pandemic H1N1 2009 virus. See below for a detailed laboratory surveillance update.
About pandemic flu
• Last modified date:
1 May 2009
A pandemic is a global disease outbreak. Pandemic flu occurs when a new influenza virus emerges for which people have little or no immunity, and for which there is no vaccine. The disease spreads easily from person to person, causes serious illness and can sweep across the country in which it originates and around the world in a very short time.
In contrast to the ‘ordinary’ or ‘seasonal’, flu outbreaks which we see every winter in the UK, flu pandemics occur infrequently - usually every few decades. There were three last century. The most serious was in 1918, killing millions of people worldwide and smaller pandemics happened in 1957 and 1968.
Are we at risk now?
A pandemic can only start when three conditions have been met:
• a new influenza virus subtype emerges
• it infects humans, causing serious illness
• it spreads easily and sustainably among humans.
When will a pandemic arrive in UK?
We do not know – it can’t be predicted. The gaps between previous pandemics have varied widely. Intervals between previous pandemics have varied from 11 to 42 years with no recognisable pattern. Three influenza pandemics occurred in the last century – 1918/19 (Spanish flu), 1957/58 (Asian flu) and 1968/69 (Hong Kong flu). All affected large numbers of the population, causing many deaths and huge economic and social disruption.
How long will it take to arrive in the UK?
Probably less than six months and possibly just a few weeks or less, but this will depend upon where the pandemic emerges. Of course, it is important to remember that the pandemic could emerge in the UK. The increasing speed and volume of modern travel means infectious diseases can travel very rapidly around the globe.
Can it be prevented at any stage?
International effort will be made in trying to control a pandemic when it emerges. However, influenza is highly infectious and because whole populations will be susceptible to the new virus, despite people’s best efforts, it is likely to continue to spread.
The World Health Organisation (WHO) has purchased a stockpile of antivirals which can be transported to the source of the outbreak. It is hoped that these antivirals may help to contain the emerging virus.
Who is at risk?
We cannot know which groups will be affected by pandemic flu until the virus emerges. However, we know from previous pandemics that a future one is likely to have a major impact worldwide and from experience of previous pandemics we know that it is not necessarily the young and the elderly that will be affected.
How is the virus spread?
The virus is easily passed from person to person by breathing in air containing the virus produced when an infected person talks, coughs or sneezes. It can also spread through hand/ face contact after touching a person or surface contaminated with the virus.
Symptoms
Pandemic flu is likely to cause the same symptoms as ordinary flu but the symptoms may be more severe because nobody will have any immunity or protection against that particular virus. People infected with the current strand of the avian virus (H5N1) have shown everything from typical human influenza-like symptoms (fever, cough, sore throat, and muscle aches) to pneumonia, severe respiratory diseases, and other life-threatening complications.
Influenza
Influenza, or 'flu', is a highly contagious acute viral infection that affects people of all ages. It typically starts suddenly with fever, chills, headache, aching muscles, general prostration and a cough or other respiratory symptoms.
While most people recover without complications in 1-2 weeks, flu can cause serious illness and death, especially in the very young and the elderly.
Flu epidemics occur mainly in the winter months and can result in widespread disruption to healthcare and other services. A vaccine is produced every year based on the strains of virus expected to be circulating.
Swine flu
This section contains information related to the recent swine flu outbreak.
Pandemic flu
A pandemic occurs when a new influenza virus, which people have no immunity to, emerges and starts spreading as easily as normal influenza. The Department of Health is working to support NHS preparedness and to reduce the impact of pandemic flu on the UK population.
This is generic guidance intended to assist in preparing for a pandemic whose nature and severity is unknown. Although much of the content remains relevant in the current swine flu pandemic, some aspects, particularly those relating to at risk groups and those intended to respond to higher levels of sickness and mortality may not be applicable to the current swine flu situation. Therefore, the guidance should be read in conjunction with the latest swine flu UK planning assumptions and other specific swine flu guidance
Pandemic (H1N1) 2009 Influenza: Information for health professionals
Slowing the spread in the early stages of the current H1N1 influenza pandemic has given the HPA and the health service time to learn more about the new virus, build up antiviral and antibiotic stockpiles, and start to develop a pandemic specific vaccine.
This section contains advice and information for healthcare professionals.
Clinical diagnostic criteria
Clinicians are now encouraged to diagnose pandemic (H1N1) 2009 influenza cases on the basis of symptoms.
The clinical diagnostic criteria are:
• Fever [pyrexia ≥38°C] or a history of fever,
AND
• influenza-like illness (TWO OR MORE of the following symptoms: cough; sore throat; rhinorrhoea; limb or joint pain; headache; vomiting or diarrhoea) OR
• severe and/or life-threatening illness suggestive of an infectious process
More information can be found in the Department of Health's swine flu clinical package.
Testing
There is no need to test patients in primary care or emergency departments where admission is not required.
Testing should only be considered if patients are hospitalised, for the control of infection in hospitals, as part of 'spotter' surveillance schemes, or if there are unusual syndromes that are considered to have an infectious basis.
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