The complexities of flu in the summer time - where does it go?

Publishing in the journal, PNAS, (free paper here) a group of researchers have uncovered the secrets to the success of influenza viruses in the human population. Using extensive genetic analysis from isolates collected across the world they were able to - for the first time - understand the global dynamics of flu evolution as it makes its way from country to country and year on year.

By building large phylogenetic trees and mapping these on to each country, the group show that rather than staying put in each region every year, influenza makes its way around the world, never staying in one place too long. This they call a 'temporally structured metapopulation', and it is this which is the key to the virus's success by allowing it a continuous presence within our population. These results go contrary with what has been put forward for flu in the past, but where does the virus hide out?

Are microbes evolving to escape vaccination?

What if all those vaccines - those ones that work really well - all stopped working? Imagine if the viruses and bacteria from which they are trying to protect you against, evolved and adapted to life in a largely immune population? Those robust antibody and T cell responses generated within a person following vaccination supply the perfect breeding ground for the selection of resistant mutants where anibodies can no longer recognise and neutralize their targets and where T cells fail to eliminate infected cells. So, is it possible and is it happening?

Well, we already know this kind of phenomenon from influenza, right? Every year we have to change the strains that are put into your flu jab to match those viruses predicted to be circulating come winter. This is based on generating an antigenic match of vaccine to wild virus; specifically, their surface HA proteins must look the same. This is why there has been such a push to develop universal influenza vaccines capable of immunizing people against all flu strains. For viruses like measles and mumps however, we have our universal vaccine, or at least we thought we did.

Influenza may change through antigenic drift and shift forcing us to develop new vaccines each year, but do other viruses evolve through antigenic drift and force us to generate improved vaccines for them? http://news.bbc.co.uk/

Revisiting the origins of contagion - the measles story

The mechanisms behind the incredible infectiousness of measles are poorly understood - that is, until now, where two studies have now come forward investigating the molecular biology of measles person-person transmission. Two groups have independently identified the protein, nectin-4 (a cell adhesion molecule) as the receptor allowing measles to infect and emerge from the respiratory tract and spread from person to person, potentially filling in a major gap in our understanding of this important human pathogen.

The measles virus is one of - if not the most - infectious agents currently circulating in human populations. It is also responsible for considerable disease and death worldwide, particularly across the developing world. But luckily, the introduction of a live-attenuated vaccine has significantly reduced it's incidence - this is in spite of a number of recent outbreaks associated with reduced vaccination rates. 

Mumps outbreaks - why here, why now? and how can we stop it?

Mumps is an acute viral disease of humans and really only humans. It is spread through the respiratory tract (probably droplets and aerosols) where the virus most likely infects the cells lining the epithelium - we don't really know this for certain. From here it spreads throughout the body, infecting organs and tissues such as the salivary glands, testes and ovaries, pancreas, and perhaps most worryingly, your central nervous system. In fact, in the pre-vaccine era, mumps was the biggest cause of aseptic meningitis across the developed world; it can also cause the more severe encephalitis.

Lucky we've got a vaccine, right?

What's in a cough? Viruses. Lots of viruses.

A cough - Tang et al 2008

Respiratory pathogens are pro's when it comes to person-person transmission; easy in and easy out. Viral replication - and also I guess bacterial - followed by the subsequent immune response, induces a range of behaviors in the host which results in the expulsion of doses of infectious particles. These include your runny nose, coughs and sneezes -  you've all experienced them. Although even talking and breathing may also be spreading virus.

But, how exactly does the virus cause this? Which mechanism is potentially the most potent transmitter of virus? How many particles can be found in your average cough? And, how do these behaviors physically transfer infection? Perhaps most important - what can we do to stop it?

Did dinosaurs get measles?

 I know what you're thinking: of course they did - what organism out there isn't parasitized by viruses and their ilk? But where's the evidence? In science you can't just pluck ideas out of the air like this - no matter how obvious they are - and say they are true; maybe dinosaurs had a fantastic immune system and were able to thwart any potential viral invaders. What I'm saying is that we just don't know, but a paper published last month in Current Biology suggests otherwise: documenting the discovery that some dinosaur (see above) fossils bare lesions in their bones that are suggestive of viral infection.

Why don't we have a #dengue vaccine yet?

This is taken from a recent special issue of the journal Vaccine from September covering the "state-of-the-art" of dengue virus vaccine research. 

The process of generating - and testing -  a dengue vaccine captures the entire field of vaccinology and highlights it's promises and pit-falls and can be used as a model when thinking of any number of potential vaccine initiatives.

See below for my take and summary of this issue:

What can flies tell us about #virusevolution?

Some of the fly species used in this study (thanks to Ben Longdon).

 What influences whether a parasite - for example a virus - will infect a new host and jump species? Is it more to do with the virus, or the host? Maybe something entirely different, like whether the two hosts will ever meet. Investigating these factors may allow us to predict how viruses will behave in their natural environment and aid us in determining the likelihood of transmission and spread into - and throughout - a new species, like us, humans. Imagine if we had had this knowledge earlier, we may have been able to prevent such epidemics HIV, SARS or the recurring ebola outbreaks. 

 Well, this is exactly what one group - joint between Edinburgh and Cambridge Universities in the UK - are doing. Get the PLoS Pathogens paper here. Using perhaps the only experimentally amenable model system for animals - which consisted of flies and their viruses - they recently provide evidence that the likelihood of a virus replicating within a new host has a lot to do with how genetically related it is to the original host species. And, surprisingly, in some cases it has not much at all to with it - further compounding the complexities of virus emergence. But how did they do it?

#vaccines - can you predict how well they'll work?

 

Vaccines are great aren't they -  they offer us probably the most cost-effective means of reducing death and suffering on a worldwide scale that extends to both humans and other animals. The problem is that it's never been as easy as just dreaming up a vaccine for the latest virus to afflict us. Effective vaccines are extremely difficult to produce, even for the most well-researched pathogens and, even when you do develop one, plow billions into it's generation and testing, and get it successfully through all the necessary clinical trials it still might not work so perfectly. 

Your liver as a viral filter - who, what, where, why?

The liver is a pretty amazing organ (see structure above) - especially when you take into account its often unrecognised immunological role. It's becoming more established that we can kind of think of the liver as a giant biological filter where it extracts all sorts of harmful molecules and pathogens from our blood. After all, it is a major component of the reticuloendothelial system - your bodies natural filtering system. From the minute any microbe reaches your blood stream, it is instantly taken to the liver on the back of our circulatory system. And, within an hour, nearly 100% of those pathogens are removed (see graph below) but what is doing this inside your liver? 

But, while this all sounds like a pretty good idea, removing those nasty viruses - when we move into the administration of viral gene therapy vectors, what we don't want is the liver to remove those helpful microbes. And it's becoming a pretty big research project, trying to engineer these vectors to evade our liver.

The system isn't perfect but how exactly does it work? - and if we understand how it works, can we subvert it?