Viruses at the crossroads of infection

Last week I wrote about a recent paper showing that in some cases influenza viruses can escape from the lungs of an infected person; here, it makes it's way to the local lymph nodes by infecting your lung's sentinal immune cells, the dendritic cells. In this instance, this mechanism is probably being used by our own body's as a defence: by capturing influenza virus in the lung we can kick start our immune system by handing it directly to T and B cells within the lymph nodes. But it can also have deadly implication, especially considering that possibly every virus will have some run in with a dendritic cell during an infection.

**for a great discussion of what goes on inside lymph nodes during the induction of an immune response, see last weeks This Week in Virology**

Complicated diagram of the role of dendritic cells in the immune response. On the left, DC's grab antigen (for example a virus) and thus move into nearby lymph nodes. Here they present antigen to T cells ( or B cells). These cells leave the lymph nodes to hunt down their specific antigenic target (shown on the right here whether the T cells move into infected tissues. What DC's can also do is carry infectious viruses into the lymph nodes where they are free to replicate inside the dense population of T and B cells. http://www.biken.osaka-u.ac.jp/COE/eng/project/images/fig-hirata-jpg.jpg

Influenza - putting the Trojan into the horse but should you open it?

A trojan horse (dendritic cell) filled with virus

Inspired by a recent journal club article:

A number of pathogens infect via one organ but are able to move to another. Think of the likes of the initial HIV infection of cells within the reproductive tract followed by its transfer to the immune system (see my earlier post here). This transfer of viruses, bacteria or other parasites is responsible for the induction of an effective immune response but also it can lead to some of the more serious disease symptoms during infection, but how is it controlled?

MolBio Carnival #17!

Apolipoprotein AI

That's right, its time for the 17th installment of the molecular biology carnival where we celebrate and discuss the science and implications of molecular biology research through those blog posts that contributors have put forward. This months installment will take a microbiological twist, fitting for the blog it is hosted at. So lets see what we have. 

Proteins are amazing, especially microbial ones that cause disease.

First up - with a somewhat non-micro focused post - but nonetheless interesting, Mike Tyka over at 'Beautiful Proteins' shares with us the Mobius strip-like folding of the human apolipoprotein A-I, a protein that has a role in the pathogenesis of Alzheimer's disease. See opposite.

But how do we study these molecules? Here's S.E.Gould over at Lab Rat with her post 'How to explore a protein' whereby she takes us on the constant journey of discovery that scientists begin when they want to understand how a protein works.

It’s a nice short little paper but it does bring up some interesting points and also works as a prime example of a very common way that scientists go about exploring how a particular protein works.

 James Byrne, of Disease Prone fame shares with us the fascinating world of bacterial toxins, molecules (peptides/proteins) that are synthesized by a number of disease-causing microbes in order to allow for their survival following infection. He includes the science behind Botox, deadly E.coli and pneumonia. 

Key to the development of disease in many bacterial infections is expression of a bacterial toxin. Toxins come in many shapes and forms but all have a pretty similar goal, to directly induce damage to the cells of the host.

But understanding microbial evolution through DNA and RNA is also important

Yersinia pestis - a deadly human pathogen. But how did it spread across the world and cause disease? Only it's DNA has the answer.

One important process in microbial biology and evolution is conjugation, the physical transfer of genetic material between two prokaryotic cells. It is this which is responsible for the rapid spread of antibiotic resistance genes throughout a given environment. 

The donor has the plasmid with the gene that confers antibiotic resistance, and the recipient doesn't. Once the donor "recognizes" that the nearby cell lacks the resistance gene, a channel gets opened from the donor cell to the recipient.

But what controls whether one cell will give its DNA to the other? How does it know that it lacks the antibiotic resistance gene? Turns out it - as EE Giorgi at 'Chimeras' shows, is down to transcription. They also discuss the role of so-called 'junk DNA' in genome biology through a series of blog posts.

 The important understanding of how pathogens evolve throughout the course of a single infection, outbreak or even over hundreds of years is underpinned by he study of DNA itself. Michelle Ziegler from 'Contagions' gives us two amazing examples of how looking at Yersinia pestis (bacteria behind plague/black death) genes themselves can tell us so much about the history of it's disease outbreaks. She asks: Did India and China escape the black death? and discusses the recent full genome sequencing efforts from bacteria found in a UK plague grave site.

The Black Death (1347-1352) draws all the attention because of its scope and scale, the amount of evidence, and the intensity of its legend. In some parts of the world, legend is nearly all we have (or have so far). Although the scientific evidence points toward an Asian origin for Yersinia pestis, there is precious little documentary evidence of it in Asia before modern times (17th century onwards).

How can we stop these microorganisms causing death and disease?

MHC 1 pathway. Wikipedia.

Next we have Becky Ward over at 'It takes 30' in her post 'Windows on the cellular soul' discussing the applications of high-throughput mass spectrometry in understanding the systems biology of the MHC1 'immunopeptidome' (the 'natural' means of controlling infection) and what it tells us about what is going on inside the cell. Remember that these 'major histocompatability complexes' direct the immune response against intracellular bacteria, viruses and parasites.

One of the things we wonder about a lot in biology is what is going on inside a cell.  We have many ways to get at partial answers — Western blots, GFP fusions, transcriptional profiling, various proteomic techniques — and the number and power of these approaches is increasing. Here’s a new window on the internal state of a cell that makes use of a fundamental process of biology: the presentation of peptides by the class I MHC complex

 

Sometimes our own immune system can't beat the invaders, so we now have with two posts from Nsikan Akpan at 'That's BS. !!!' showcasing our medical fight against these disease-causing bacteria (Chlamydia vaccine) AND viruses (small molecule inhibitor of Ebola virus entry).

The days might be numbered for one of Africa’s most dangerous contagions – the Ebola virus. Two studies from the journal Nature have revealed how this virus breaks into our cells. Turns out that Ebola hitches a ride on a “cellular highway” normally reserved for cholesterol.

But lets remember, microbes aren't always bad:

And, to round it off, we have Suzanna Elvidge (at www.genome-engineering.com/) remembering Lynn Margulis following her recent death. Lynn put forward the theory of endosymbiosis in the establishment and evolution of eukaryotes from a prokaryotic assemblage while she also denied the role of HIV in AIDS. You win some, you lose some. 

Lynn Margulis (1938-2011). From Wikimedia.

So that's it for MolBio #17 over at Ruleof6ix. If you're interested in being a part of the next edition: submit your blog article using our carnival submission form. Past posts and future hosts can be found on our blog carnival index page.

**The next edition will be out at http://chimerasthebooks.blogspot.com/
hosted by E.E. Giorgi and it'll be on the first Monday in January.

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.