Skip to 0 minutes and 13 seconds In this short video, we’re going to look at other viruses that are often mistaken for influenza. Throughout this course, we’ve been discussing influenza A. As we’ve seen, this is a virus that exists in many bird populations, especially migratory wild fowl, meaning ducks and geese with a very high diversity of subtypes. A subset of these subtypes have found their way into other species like pigs, humans, or horses from time to time, usually by complex reassortment events. Once in the other species, they initially cause pandemics, and then seasonal flus. Some seasonal flu subtypes can remain in human populations for several years. H3N2 has been with us, causing much misery every winter, since 1968.
Skip to 0 minutes and 58 seconds Influenza A is the most important type of influenza, from both clinical and agricultural viewpoints. But it isn’t the only type of flu. Influenza B and influenza C are related species. And together with influenza A, they’re part of the family orthomyxoviridae. The word “family” is used here as a taxonomic term. Taxonomy is the science of biological classification. And it’s applied to all kinds of life. For instance, domestic cats are the species Felis catus, and they belong to the family Felidae, along with their larger relatives, lions and tigers. The family orthomyxoviridae that contains the three influenza viruses also contains the isaviruses, which infect fish, the quaranjaviruses, and thogotoviruses.
Skip to 1 minute and 46 seconds The last two groups are spread by blood sucking ticks, which transfer the virus while biting their animal and human hosts. This demonstrates how related viruses can cause a wide range of different diseases, and in different hosts. Influenza B can be quite severe, and because of this, it is also included in the annual seasonal flu vaccine. Unlike the main kind of influenza, influenza A, which we’ve been discussing entirely up until now, influenza B doesn’t appear to have an avian reservoir host population. In fact, the main host for flu B seems to be us. It’s been found in a few domestic animals very occasionally and also in seals.
Skip to 2 minutes and 29 seconds Now, whether this means that humans are the main reservoir of influenza B or that there’s a yet undiscovered animal reservoir remains to be seen. Likewise, influenza C is predominantly a human disease, but has been found also in pigs and cattle. Since the cultural strains of influenza C are often rather different to the human ones, there’s been some talk of creating a new species definition, influenza D, to include them, but this is not yet official. Flu C has historically been regarded as a milder strain of flu than A or B, and has therefore never been included in a vaccine. However, it’s now recognised as a cause of pneumonia in infants and could be more important than we’ve so far acknowledged.
Skip to 3 minutes and 13 seconds Unlike influenza A, flus B and C do not have a large diversity of subtypes. There’s no equivalent of the H1N1 or H3N2 nomenclature that we see in flu A. For flu B, we just divide strains into two general categories named Yamagata and Victoria, after the places where they were first isolated in the late 1980s. Usually, either Yamagata or Victoria group strains will be dominant in any particular year. For flu C, there’s a lot less information, since, unlike A and B, it’s not in the vaccine and so consequently, less intensive monitoring efforts take place. However, we do know that for both influenza B and influenza C, there’s a lot of reassortment, and that reassortment occurs in humans.
Skip to 4 minutes and 2 seconds This contrasts with influenza A, where reassortment in humans is a rare event, and usually, when it occurs, with serious consequences. In B and C on the other hand, reassortment does not necessarily produce new strains with increased virulence. Influenza C is also a little different to A and B in that it has only seven segments instead of eight. At some point in influenza C’s ancestry, after it separated from the ancestor of A and B, there must have been a segment fusion event. Flu C has a single haemagglutinin-esterase protein instead of separate haemagglutinin and neuraminidase proteins found in its relatives. Many people who catch a heavy cold in the autumn or early winter might feel that they have the flu.
Skip to 4 minutes and 50 seconds However, usually, that conclusion is incorrect. The true influenza season begins at a variable time each year. But for the majority of years in the northern hemisphere, influenzas A and B begin to arrive in January. We have much less information about influenza C, which may not be as seasonal as the others. So it is possible that you can have flu in the northern hemisphere before Christmas. But it’s rather more likely after Christmas. There are plenty of other viruses, however, that can give you that flu-like experience. One of the most important is respiratory syncytial virus, or RSV, which can cause particularly bad problems in children. Research into vaccines for RSV is a very active area of research.
Skip to 5 minutes and 36 seconds RSV is a pneumovirus, and is part of the family paramyxoviridae. Now, despite the similarity in name, they’re a bit different viruses of the family orthomyxoviridae, to which our flu viruses belong. One major difference is that paramyxoviruses have a single genome instead of the segmented genomes of orthomyxoviruses. So there’s no reassortment in respiratory syncytial virus. Also in the same family as RSV are a cluster of viruses called parainfluenza viruses. These infect humans and some other animals. In fact, parainfluenza virus type five is the main cause of kennel cough, which you might have heard of if you’re a dog owner. However, don’t be misled by the name parainfluenza virus. This isn’t a true flu virus.
Skip to 6 minutes and 26 seconds And in fact, its closest relative is mumps virus. In 2003, there was an outbreak of severe acute respiratory syndrome, or SARS, in China that spread to several other countries and caused some considerable alarm at the time. More recently, Middle East respiratory syndrome, or MERS, has been causing problems in Saudi Arabia, and seeding outbreaks in other countries, most notably in Korea in mid-2015. SARS and MERS wouldn’t really be confused with influenza for long clinically, as they attack the lungs very aggressively and rapidly progressed to pneumonia, which is only a rare complication in the flu. But they are interesting in that they belong to the family coronaviridae, which also has several viruses that cause cold or flu-like symptoms.
Skip to 7 minutes and 15 seconds Another family that, like the coronaviridae, contains viruses causing flu-like and non flu-like symptoms is the picornaviridae, especially the group within them called the enteroviruses and the rhinoviruses. “Rhino” is Greek for “nose,” but “entero” for “intestine,” which might suggest that enteroviruses are more prone to cause gastric upsets. However, the naming system is largely an accident of history. Enteroviruses can spread via respiratory and gastrointestinal routes, even if their main symptoms are those of a heavy cold or flu-like illness. Among the enteroviruses, however, we also find things like poliovirus, which cause a very distinct disease of their own.
Skip to 8 minutes and 0 seconds Of course, in most cases, we never get to find out what is causing us to suffer our flu symptoms, whether it’s a real influenza virus of the A, B, or C types, a coronavirus, an enterovirus, a rhinovirus, or respiratory syncytial virus, one of its relatives, or something else entirely. We mostly have to just suffer and wonder. Only if we’re very ill and end up in hospital will a test possibly be contemplated. That however, may soon change thanks to a new technology called a deep sequencing. Deep sequencing is the latest acceleration of the technology of the Human Genome Project.
Skip to 8 minutes and 39 seconds Using deep sequencing, we can currently obtain genome sequences about 100 times faster than we could at the turn of the millennium, and also about 100 times cheaper. Now, this technological advance has given rise to a new science called metagenomics, which aims to sequence clinical and environmental samples that are mixtures of many different things. These could be anything from soil samples, deep ocean sea water, snow from a mountain top, the droppings of an animal, or perhaps a sample of our mucus when we have the flu. On completion of the metagenomics deep sequencing, we have a list of all the organisms that are in there.
Skip to 9 minutes and 18 seconds For a nasal swab from a flu patient, we would typically find a lot of that patient’s DNA, plus perhaps some of the bacteria that commonly live in the nose, like streptococci, and also whatever viruses are in there. Metagenomics may one day be so cheap and fast that if you go to the doctor with a cold, a sample will be taken on the spot, and the precise cause of your symptoms be identified the same day. You may then be more accurately guided as to how to treat your illness. Doctors will then be able to reduce the amount of antibiotics that are prescribed unnecessarily. The future will undoubtedly bring better treatments, better vaccines, and better diagnostics.
Skip to 9 minutes and 57 seconds We have reasonable grounds to believe that some of the misery of influenza might be reduced. Although, of course, not everybody will be able to afford these things, at least until the cost of new technology comes down. But the flu will probably never go away completely. The next pandemic is coming. The only uncertainty is when.
Flu B and C
Almost all the discussion in this course has been about influenza A. In this video we’re going to think about all the other viruses that can give us cold or flu-like symptoms.
Influenza B was briefly mentioned in the interview with Rhiannon Edge about her research on vaccination, but we’ll be looking at it more closely here, as well as influenza C.
Flu B is included in the annual vaccination, and comes in two varieties: Victoria and Yamagata. These variants can be considered as being like the subtypes of influenza A, although they are rather more closely related to each other than flu A subtypes.
Just as flu A subtypes H1N1 and H3N2 can have incidences wax and wane from season to season, so do Victoria and Yamagata seem to compete with each other, some years being Victoria years and others Yamagata years - with the occasional dual year.
Influenza “C” could well stand for “Cinderella”, since after being ignored for many years, flu C is finally “coming to the ball”. From 1946 to 1989, the UK Medical Research Council sponsored a research centre called the Common Cold Unit where viruses were administered to volunteers and their symptoms catalogued.
In 1968 a study was performed in influenza C virus which concluded that its clinical impact was no worse than a typical heavy cold. As a result of this, flu C was neglected and researchers pursued the more pressing agenda of influenzas A and B.
The revival of interest in influenza C has been due to the observation that it is often detected in infants with pneumonia. The original 1968 study used only healthy adults, who had probably encountered influenza C as children and had some prior immunity.
My student Kate, who appears in the nasal swabbing video, has been collecting samples over the winter of 2014-2015 in the Lancaster area to investigate the prevalence and evolution of influenza C.
Some links to further reading can be found below.
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