72 posts · 103,738 views
Connor is a PhD student from Northern Ireland studying at Queens University, Belfast. He is interested in the molecular determinants of viral pathogenesis and how we can apply its understanding to the development of novel therapeutics. He is attempting to get his head around viruses in general with this blog.
The new meningitis B vaccine developed by Novartis has just been approved by the European Medicines Agency. their approach to the vaccine production was completely different from the traditional method of making vaccines. So how can we harness this to make it easier and cheaper in the future for other human pathogens?... Read more »
Serruto D, Bottomley MJ, Ram S, Giuliani MM, & Rappuoli R. (2012) The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens. Vaccine. PMID: 22607904
What cased a nearly 4,000-large outbreak of mumps virus in the state of New York (2009-2010) to predominantly infect those who had been vaccinated with two doses of the MMR? The CDC narrows it down to orthodox Jewish schooling. But how exactly?... Read more »
Barskey, A., Schulte, C., Rosen, J., Handschur, E., Rausch-Phung, E., Doll, M., Cummings, K., Alleyne, E., High, P., Lawler, J.... (2012) Mumps Outbreak in Orthodox Jewish Communities in the United States. New England Journal of Medicine, 367(18), 1704-1713. DOI: 10.1056/NEJMoa1202865
The use of new high-resolution imaging techniques to break the diffraction barrier and observe biological processes of viruses hiding from us in plain site. Case in hand: HIV glycoprotein regulation.... Read more »
Chojnacki, J., Staudt, T., Glass, B., Bingen, P., Engelhardt, J., Anders, M., Schneider, J., Muller, B., Hell, S., & Krausslich, H. (2012) Maturation-Dependent HIV-1 Surface Protein Redistribution Revealed by Fluorescence Nanoscopy. Science, 338(6106), 524-528. DOI: 10.1126/science.1226359
The second paper in the Microbiology Twitter Journal Club (Tuesday the 22nd May 2012) is the paper out last year documenting the sequencing and assembly of the complete genome of a strain of Yersinia Pestis (plague) from a 14th Century burial site. It's open access so check it out here.
... Read more »
Bos, K., Schuenemann, V., Golding, G., Burbano, H., Waglechner, N., Coombes, B., McPhee, J., DeWitte, S., Meyer, M., Schmedes, S.... (2011) A draft genome of Yersinia pestis from victims of the Black Death. Nature, 478(7370), 506-510. DOI: 10.1038/nature10549
It was recently reported - at the National Foundation for Infectious Diseases 15th Annual Conference on Vaccine Research - that the rate of adverse effects from a third dose of the measles, mumps and rubella (MMR) vaccine is the same as those of the second dose. The study has some obvious caveats but what it brings up is the question of whether we should extend 3-dose coverage to the population as a whole?... Read more »
Centers for Disease Control and Prevention (CDC). (2010) Update: mumps outbreak - New York and New Jersey, June 2009-January 2010. MMWR. Morbidity and mortality weekly report, 59(5), 125-9. PMID: 20150887
RSV is an extremely common respiratory infection of humans. In adults it causes little disease but in newborns and the elderly it can lead to deadly complications. Here is my interview with one researcher is trying to understand how and why this virus infects your lungs and causes disease.... Read more »
Villenave, R., Thavagnanam, S., Sarlang, S., Parker, J., Douglas, I., Skibinski, G., Heaney, L., McKaigue, J., Coyle, P., Shields, M.... (2012) In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. Proceedings of the National Academy of Sciences, 109(13), 5040-5045. DOI: 10.1073/pnas.1110203109
I am sure you have heard of Wipfelkrankheit disease. If you haven't heard of this name at least you must have heard what it's symptoms are. Wipfelkrankheit - or in English, tree-top disease, is a fatal viral infection of caterpillars, an infection that causes them to climb up high, hang upside down and liquify themselves raining down millions upon millions of viral particles to the forest floor below. ... Read more »
Katsuma, S., Koyano, Y., Kang, W., Kokusho, R., Kamita, S., & Shimada, T. (2012) The Baculovirus Uses a Captured Host Phosphatase to Induce Enhanced Locomotory Activity in Host Caterpillars. PLoS Pathogens, 8(4). DOI: 10.1371/journal.ppat.1002644
What's that big brown bag - packed full of red blood cells - for in the upper left of your chest? Sure you can live without it but why's it there in the first place and what's it doing for you? You wouldn't just be carrying round that extra 175g (for an 'average' person) just for nothing would you? While it has been known that loss of your spleen, or asplenia has some pretty strange effects, such as an increase in some blood cells, lessened response to vaccinations and an increased risk ........ Read more »
Honke, N., Shaabani, N., Cadeddu, G., Sorg, U., Zhang, D., Trilling, M., Klingel, K., Sauter, M., Kandolf, R., Gailus, N.... (2011) Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nature Immunology, 13(1), 51-57. DOI: 10.1038/ni.2169
Prion protein in red on dendritic cell beside neuron (green)
This blog focuses on trying to understand how viruses cause disease in their hosts - whether they be single cells or us, humans. Attempting to do so means that we must look at how viruses enter these hosts, survive within the hostile environment that is another organism and eventually make their way on to infect the next one. One thing this blog doesn't do, is look at how other kinds of pathogens complete this complex life cycle.
........ Read more »
Castro-Seoane, R., Hummerich, H., Sweeting, T., Tattum, M., Linehan, J., Fernandez de Marco, M., Brandner, S., Collinge, J., & Klöhn, P. (2012) Plasmacytoid Dendritic Cells Sequester High Prion Titres at Early Stages of Prion Infection. PLoS Pathogens, 8(2). DOI: 10.1371/journal.ppat.1002538
Still-born lamb after Schmallenberg infection. http://www.augsburger-allgemeine.de/i
Europe is currently experiencing an incredibly worrying outbreak of disease across hundreds of farms in the North-West and it has finally popped up in the UK. The disease - caused by a previously unknown virus - has been causing a large number of still births in cows, goats and sheep after it was initially found in the Netherlands and Germany. What is worrying about this is our economic dependance on this ki........ Read more »
Measles, that deadly childhood infectious disease is almost a distant memory to most people nowadays, that is except for a few isolated outbreaks across the US and Europe. This is all because of a really amazing preventative therapy: the vaccine.
Vaccines are great. They are by far the most effective means that we have to control - and hopefully eradicate - infectious diseases from a range of species. Measles is one of these diseases that, over the last half a decade or so, we have backed........ Read more »
Poland GA, & Jacobson RM. (2012) The re-emergence of measles in developed countries: Time to develop the next-generation measles vaccines?. Vaccine, 30(2), 103-4. PMID: 22196079
This is something I would like your input on:
How important is strain choice in virus/microbiology research?
Does it differ with certain aspects of research, like pathogenesis versus structural studies?
How far do we discount studies done on less 'wild-type' viruses?
How come people are happy working with these viruses?
We microbiologists uncover the secrets of how microbes interact with their hosts in order to better understand the infection process. We can use this........ Read more »
Othumpangat, S., Walton, C., & Piedimonte, G. (2012) MicroRNA-221 Modulates RSV Replication in Human Bronchial Epithelium by Targeting NGF Expression. PLoS ONE, 7(1). DOI: 10.1371/journal.pone.0030030
Measles virus - is it targeted by an HIV restriction factor?
Cellular organisms have evolved multiple defences to keep viruses and other genetic parasites at bay. One such shield is the development of an advanced adaptive immune system seen in vertebrates while another is the more evolutionary widespread 'innate' system made up of various expressed proteins and small RNAs. These molecules prevent particular stages of the viral replication cycle like entry, replication or exit.
Anot........ Read more »
Fehrholz M, Kendl S, Prifert C, Weissbrich B, Lemon K, Rennick L, Duprex PW, Rima BK, Koning FA, Holmes RK.... (2011) The innate antiviral factor APOBEC3G targets replication of measles, mumps, and respiratory syncytial virus. The Journal of general virology. PMID: 22170635
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 serio........ Read more »
Moltedo, B., Li, W., Yount, J., & Moran, T. (2011) Unique Type I Interferon Responses Determine the Functional Fate of Migratory Lung Dendritic Cells during Influenza Virus Infection. PLoS Pathogens, 7(11). DOI: 10.1371/journal.ppat.1002345
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 st........ Read more »
Bahl J, Nelson MI, Chan KH, Chen R, Vijaykrishna D, Halpin RA, Stockwell TB, Lin X, Wentworth DE, Ghedin E.... (2011) Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans. Proceedings of the National Academy of Sciences of the United States of America, 108(48), 19359-64. PMID: 22084096
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 elimina........ Read more »
Rubin SA, Link MA, Sauder CJ, Zhang C, Ngo L, Rima BK, & Duprex WP. (2011) Recent mumps outbreaks in vaccinated populations: no evidence of immune escape. Journal of virology. PMID: 22072778
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 im........ Read more »
Mühlebach, M., Mateo, M., Sinn, P., Prüfer, S., Uhlig, K., Leonard, V., Navaratnarajah, C., Frenzke, M., Wong, X., Sawatsky, B.... (2011) Adherens junction protein nectin-4 is the epithelial receptor for measles virus. Nature. DOI: 10.1038/nature10639
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........ Read more »
Cortese MM, Barskey AE, Tegtmeier GE, Zhang C, Ngo L, Kyaw MH, Baughman AL, Menitove JE, Hickman CJ, Bellini WJ.... (2011) Mumps antibody levels among students before a mumps outbreak: in search of a correlate of immunity. The Journal of infectious diseases, 204(9), 1413-22. PMID: 21933874
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 ........ Read more »
Lindsley, W., Blachere, F., Thewlis, R., Vishnu, A., Davis, K., Cao, G., Palmer, J., Clark, K., Fisher, M., Khakoo, R.... (2010) Measurements of Airborne Influenza Virus in Aerosol Particles from Human Coughs. PLoS ONE, 5(11). DOI: 10.1371/journal.pone.0015100
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: document........ Read more »
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