Skip to 0 minutes and 14 secondsIn this short video, we'll take a look at the biology of the influenza virus. Viruses are very small. If you view a drop of water in strong light, you might be able to see small specks of dust floating in the water. The smallest dust particles visible to the human eye are around 50 microns in diameter. A micron is the same as a micrometre, or 1,000th of a millimetre. An oocyte, that's a human egg, is also around 50 microns. However, most cells in the human body are considerably smaller. A red blood cell, for instance, is fairly typical, being around 7 microns across. But viruses are smaller still.
Skip to 0 minutes and 52 secondsEven the largest virus is barely a single micron in size, and many are smaller. Flu viruses are around 1/10th of a micron across, or 100 nanometres. That's 500 times smaller than the smallest speck of dust visible to the human eye. This is too small even to be seen with the most powerful conventional microscopes so in virology, electron microscopes are used. These fire tiny charged particles, electrons, onto the object they're imaging and reconstruct a representation from what bounces back at them. Viruses are pure parasites. They can only exist by hijacking the processes of the cells they infect.
Skip to 1 minute and 32 secondsWhen you have a virus, it's your cells that are doing all the work of running the virus life cycle and making new copies of the virus to further infect you and other people. This contrasts with disease-causing bacteria, fungi, and protozoa, which are small cells in their own right, carrying out most of the basic processes that our cells do. Viruses, on the other hand, have none of this. And it's possible to consider them as not even really being alive at all, but rather as molecular machines, inert entities that float around doing nothing until they chance across another potential host, at which point they're activated. Viruses can have many weird and wonderful shapes.
Skip to 2 minutes and 13 secondsPerhaps the oddest of all are the bacteriophages, which look like spacecraft from a 1950s sci-fi movie. The flu virus, on the other hand, isn't one of the more spectacular ones. Bacteriophages, as well as having really striking appearances, also have a dramatic life cycle, replicating until the host cells are full of new virus particles and then emerging in an explosive process called lysis that destroys the host cell. Influenza, however, isn't a lytic virus like a bacteriophage, but a budding virus. So new flu viruses just pop out individually from the host cell, wrapping themselves in a piece of host cell membrane as they emerge. The host cells stay alive. Sometimes, just alive. And they shed the viruses in a steady stream.
Skip to 2 minutes and 59 secondsIf a flu virus was big enough to be seen with a naked eye, the first two things we would notice is two kinds of protein protruding as spikes from the surface. These are the haemagglutinin and neuraminidase proteins. Because they're on the surface of the virus, the haemagglutinin and neuraminidase proteins are the main targets of your immune system. They're also the basis for the classification of flu viruses as subtypes, such as H1N1, H2N2, H3N2, and so on. If you suffer from an attack of H1N1, your immune system will produce lots of antibodies against the H1 variant of haemagglutinin and the N1 variant of neuraminidase. This will protect you from being infected again, at least, for a while.
Skip to 3 minutes and 42 secondsBut as the flu virus evolves, that protection will be eroded. This is the concept of antigenic drift. The H1N1 that may appear this winter will not be quite the same as the H1N1 we saw previously. And you may no longer be completely protected. However, your encounter with H1N1 will have gained you no protection at all against H3N2, as the differences between haemagglutinin in H1 and H3 are very extensive. The same applies to neuraminidase N1 and N2. Now, let's take a look at the remaining proteins in a virus. If we could break open the surface of the virus, inside we would find nucleoprotein, matrix protein, three types of polymerase, and two non-structural proteins. Nucleoprotein and matrix protein are largely structural.
Skip to 4 minutes and 29 secondsThey hold the virus and its genetic information, its genome, together. The polymerase components are responsible for making more copies of that genome. Viruses, as I said before, are pure parasites. Their life cycle just consists of invading a new host, making as many copies of themselves as possible, and then getting out in search of another new host. So our fast acting polymerase is really important to the virus. Crucially, that polymerase need not be very accurate. A lot of viruses are replicated with many mistakes in their genomes. These mistakes, their genetic mutations, are the raw material of virus evolution and the basis for antigenic drift. The two non-structural proteins have special functions.
Skip to 5 minutes and 12 secondsThe first is a counter-attack weapon against the host's immune system, and similar anti-host immune proteins are found in some other viruses, too. The second non-structural protein is involved in organising various aspects of the functions of other proteins. Although the virus has proteins that can replicate it, it doesn't have anything that can make more proteins from those genome copies. This process, called translation, is performed entirely by the host, hijacked by the virus. The host cell is co-opted into its own demise, accepting viral genomes as if they were a normal part of itself and producing vast quantities of viral proteins. These proteins, and the viral genome copies produced by the viruses' own polymerase, are packaged into millions of new virus particles.
Skip to 6 minutes and 1 secondThe genome of the flu virus is segmented, meaning that each protein is encoded on its own little fragment of genome. The exception is the two non-structural proteins, which share a segment. So there are therefore eight genome segments for nine proteins. Once we understand this, we can see how reassortment occurs and how this produces new pandemic flu strains. Today, we've looked at the molecular anatomy of the influenza virus.
Dissecting the Influenza Virus
As you watch this video, try to imagine the influenza virus blown up to gigantic size, as something you could hold in your hands and manipulate. Try to think of it as a molecular machine - a robot is a good analogy - a machine for invading your cells and making copies of itself.
The sheer strangeness of viruses is one of the attractions of studying them. We tend to imagine that we large multicellular organisms with our various tissues and organs and our complex functions and behaviours would have little in common with microscopic unicellular “bugs” like bacteria that seem to do little other than suck up nutrients from their environment and replicate themselves.
However, we actually have much more in common with bugs than we do with viruses. From the tiniest microbial cell, whether bacterial, fungal or protozoal, to the most gigantic animals and plants such as blue whales and Californian redwoods, and also humans, we are all united in the fact that we are based on cells.
Cells are little liquid spaces usually bounded by a lipid (double fat layer) membrane, or in some plants by more rigid cellulose (starchy) walls. Inside the membrane or cell wall, all the processes of biochemistry go on, which together make up the patterns we recognise as life. Bacterial life, wriggly pond life, plant life and human life are all fairly readily recognisable as being the same kind of thing - albeit at very different sizes and complexities.
Viruses, by contrast, do not have any active metabolism. There is no equivalent of the intracellular space, the watery environment where life’s processes have to go on continuously. Between hosts viruses do nothing. Inside hosts they use the host’s own life process to their own advantage - with the single goal of producing more copies of the virus.
Viruses consequently can have many different structures; the prevailing theme is the genetic material of the virus, its genome, which can be considered as a kind of instruction set for replicating itself, and the other necessary bits of virus, all together inside a shell of tightly packed proteins. Some viruses, like the bacteriophages (see 2:15) can have appendages designed to help the virus attach to its host and deliver its genome. Many people, seeing bacteriophage structures for the first time, can hardly believe what they are seeing. It is almost stranger than science fiction fantasies of “aliens”, and yet it is true.
It’s important to emphasise the fundamental difference between viruses and cellular life, but it shouldn’t be overemphasised. Once we unpack viruses, we see that their inert innards contain things that are recognisable as proteins, and which occasionally have similarities to the proteins we have in our cells. The protein diagrams you see in this video (see 3:09 onwards) are reconstructions based on X-ray crystallography, a technique which allows us to study molecular structure at the level of a few nanometers (each nanometer is 1/1000th of a micron and so 1 millionth of a millimeter).
At that level we see that viral proteins and proteins from cellular life can be studied in much the same way. Some pointers on how to interpret these diagrams are included in the accompanying lecture notes. The proteins found in influenza virus particles are:
- Haemagglutinin - important in binding the flu virus to its target cell
- Neuraminidase - important in exit of the virus from its host cell
- Acidic polymerase - part of the polymerase complex, that replicates the virus genome
- Basic polymerase 1 - likewise
- Basic polymerase 2 - likewise
- Nucleoprotein - involved in packing the virus genome into the virus particle
- Matrix protein - likewise a structural component of the virus particle
- Non-structural protein 1 - a variety of functions
- Non-structural protein 2 - likewise
Most influenza proteins are in fact quite multi-functional, and the above is only a rough guide. All are still active areas of research and there is much still to be learned. The links below provide some further reading.
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