Author Archive

A global network of researchers? Not really – small worlds.

Thursday, April 17th, 2014

As science evolves, important scientific achievements require the collaborative effort of an increasing number of researchers. The study of patterns of scientific collaboration allows us to gain further understanding of innovation and knowledge production. Scientific collaboration networks have been the subject of growing interest in the past few years. Collaborative scientific publications have a long history. The first collaborative research paper was published in 1665 in the Philosophical Transactions of the Royal Society. To date, the most multi-authored scientific paper was published in 2010, when 3,222 researchers from 32 different countries contributed to a study of charged-particle multiplicities performed in the Large Hadron Collider at CERN.

A new study finds that the United States was the country with the largest number of international collaborations, particularly with South Africa, Uganda and Brazil. The high global clustering coefficient coupled with a short average distance between nodes suggests a “small-world phenomenon” among HIV and HPV researchers. Researchers from high-income countries seem to have a high number of research collaborations among them and to cluster together in densely connected communities, particularly those from the US. There is a large well-connected community, which encompasses 70% of researchers, and other much smaller communities, including the UK.

Small worlds

International Scientific Collaboration in HIV and HPV: A Network Analysis. (2014) PLoS ONE 9(3): e93376. doi:10.1371/journal.pone.0093376
Research endeavours require the collaborative effort of an increasing number of individuals. International scientific collaborations are particularly important for HIV and HPV co-infection studies, since the burden of disease is rising in developing countries, but most experts and research funds are found in developed countries, where the prevalence of HIV is low. The objective of our study was to investigate patterns of international scientific collaboration in HIV and HPV research using social network analysis. Through a systematic review of the literature, we obtained epidemiological data, as well as data on countries and authors involved in co-infection studies. The collaboration network was analysed in respect to the following: centrality, density, modularity, connected components, distance, clustering and spectral clustering. We observed that for many low- and middle-income countries there were no epidemiological estimates of HPV infection of the cervix among HIV-infected individuals. Most studies found only involved researchers from the same country (64%). Studies derived from international collaborations including high-income countries and either low- or middle-income countries had on average three times larger sample sizes than those including only high-income countries or low-income countries. The high global clustering coefficient (0.9) coupled with a short average distance between researchers (4.34) suggests a “small-world phenomenon.” Researchers from high-income countries seem to have higher degree centrality and tend to cluster together in densely connected communities. We found a large well-connected community, which encompasses 70% of researchers, and 49 other small isolated communities. Our findings suggest that in the field of HIV and HPV, there seems to be both room and incentives for researchers to engage in collaborations between countries of different income-level. Through international collaboration resources available to researchers in high-income countries can be efficiently used to enroll more participants in low- and middle-income countries.

Where do viruses come from?

Friday, April 11th, 2014

Where do viruses come from?

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Reasons to be cheeful: Influenza treatment

Friday, April 11th, 2014

Lung immunity against influenza virus As we find out that Tamiflu is no more effective than paracetamol or ibuprofen in treating influenza infection (NHS Choices: Effectiveness of Tamiflu and Relenza questioned) – giving Ben Goldacre the right to say I told you so – maybe there is some reason to be more optimistic about treating influenza.

A new paper in Immunity [subscription] shows that prostaglandin E2 (PGE2) is upregulated during influenza A virus infection, and this inhibits macrophage recruitment to the lungs as well as interferon production and apoptosis in influenza virus-infected macrophages. This results in impaired macrophage antigen presentation and reduced adaptive immunity against influenza virus. The good news is that suppression of PGE2 with prostaglandin inhibitors protects against influenza infection. And we’ve got lots of prostaglandin inhibitors, including ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) that work by inhibiting a molecule called cyclooxygenase (COX). The lung innate immune system has a critical role in limiting respiratory viral infections, particularly in the case of the nastier strains of flu such as the 1918 Spanish Influenza virus (and those still to come). So this is potentially very good news.

The catch? Well this paper refers to studies in mice and clinical trials will need to be done in humans to show the same effects. Clinical trials will be easy to do as many COX- and PGE-inhibitors are already approved for human use. All we need to do is avoid Roche doing the trial, or we may never find out the results.

Targeted Prostaglandin E2 Inhibition Enhances Antiviral Immunity through Induction of Type I Interferon and Apoptosis in Macrophages. Immunity, 10 April 2014 doi: http://dx.doi.org/10.1016/j.immuni.2014.02.013
Summary: Aspirin gained tremendous popularity during the 1918 Spanish Influenza virus pandemic, 50 years prior to the demonstration of their inhibitory action on prostaglandins. Here, we show that during influenza A virus (IAV) infection, prostaglandin E2 (PGE2) was upregulated, which led to the inhibition of type I interferon (IFN) production and apoptosis in macrophages, thereby causing an increase in virus replication. This inhibitory role of PGE2 was not limited to innate immunity, because both antigen presentation and T cell mediated immunity were also suppressed. Targeted PGE2 suppression via genetic ablation of microsomal prostaglandin E-synthase 1 (mPGES-1) or by the pharmacological inhibition of PGE2 receptors EP2 and EP4 substantially improved survival against lethal IAV infection whereas PGE2 administration reversed this phenotype. These data demonstrate that the mPGES-1-PGE2 pathway is targeted by IAV to evade host type I IFN-dependent antiviral immunity. We propose that specific inhibition of PGE2 signaling might serve as a treatment for IAV.

[Editorial comment: I can just imaging the authors and journal editors doing the happy dance that this paper came out on sthe same day as the Tamiflu news.]

Briefing: banana disease

Wednesday, April 9th, 2014

Banana disease

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All the dirt on digital PCR

Wednesday, April 2nd, 2014

Principles of Molecular Virology Principles of Molecular Virology, Chapter 1 (Introduction to Viruses), describes the techniques used to study viruses, including bioinformatics. But molecular techniques have moved on a lot in the last few years, so the new edition will have an update on this.

I’m updating the bioinformatics section of Chapter 1 and collecting resources to illustrate recent advances in how nucleic acid technologies have moved on in the last few years. One of those advances has been digital PCR (dPCR), an amazingly sensitive technique used to measure tiny quantities in nucleic acid in clinical samples, as in this example…

Read more: Principles of Molecular Virology: All the dirt on digital PCR

How big are viruses and how many of them are there? (via xkcd)

Monday, March 31st, 2014

Pile_of_Viruses

See more: Pile_of_Viruses via xkcd

 

Exploiting bacteriophages for human health

Thursday, March 27th, 2014

Exploiting bacteriophages for human health Whenever I write about phage therapy – using bacteriophages to treat bacterial infections – readers get overly enthusiastic about injecting patients with phages to produce a miracle cure. Look at it this way – that hasn’t worked for the last 100 years and it’s not likely to suddenly start working now. This short review is worth reading because it takes a much more thoughtful and holistic approach to the idea of phage therapy than the simple minded “phage as wonder cure” idea.

Exploiting gut bacteriophages for human health. Trends Microbiol. 20 Mar 2014 pii: S0966-842X(14)00045-6. doi: 10.1016/j.tim.2014.02.010
The human gut contains approximately 1015 bacteriophages (the ‘phageome’), probably the richest concentration of biological entities on earth. Mining and exploiting these potential ‘agents of change’ is an attractive prospect. For many years, phages have been used to treat bacterial infections in humans and more recently have been approved to reduce pathogens in the food chain. Phages have also been studied as drug or vaccine delivery vectors to help treat and prevent diseases such as cancer and chronic neurodegenerative conditions. Individual phageomes vary depending on age and health, thus providing a useful biomarker of human health as well as suggesting potential interventions targeted at the gut microbiota.

HIV cure research – advances and prospects

Thursday, March 20th, 2014

HIV reservoirs Thirty years after the identification of HIV, a cure for HIV infection is still to be achieved. Advances of combined antiretroviral therapy (cART) (=HAART) in recent years have transformed HIV infection into a chronic disease when treatment is available. However, in spite of the favorable outcomes provided by the newer therapies, cART is not curative and patients are at risk of developing HIV-associated disorders. Moreover, universal access to antiretroviral treatment is restricted by financial obstacles. This review discusses the most recent strategies that have been developed in the search for an HIV cure and to improve life quality of people living with HIV.

Highlights:

  • Some cases of cure or remission of infection have boosted the search for an HIV cure.
  • cART intensification has not shown significant impact in the reservoirs, but early cART may limit them.
  • Strategies to purge the reservoirs face difficulties linked to the complexity of latency mechanisms and drug non-specificity.
  • Repression of reservoirs or cell manipulation to render them less permissive to HIV may facilitate HIV remission.
  • HIV cure/remission may require boosting immune responses while keeping inflammation in check.

 

HIV cure research: Advances and prospects. (2014) Virology pii: S0042-6822(14)00065-8. doi: 10.1016/j.virol.2014.02.021

HSV-1 evasion of the host humoral immune system

Thursday, March 13th, 2014

HSV-1 evasion of the host humoral immune system I’ve been banging on to my final year students about how clever heresviruses are at evading the immune response. No sooner do I close my mouth than another one comes along:

Herpes Simplex Virus 1 (HSV-1) infects 40–80% of adults worldwide. HSV-1 initiates infection at mucosal surfaces and spreads along sensory neurons to establish a life-long latent infection that can lead to neurological diseases. Humans usually develop IgG antibodies that specifically recognize pathogens via fragment antigen binding (Fab) variable regions. HSV-1 can avoid the protective effects of antibodies by producing gE-gI, a receptor that binds to the constant portion of IgGs (Fc), tethering the antibody in a position where it cannot trigger downstream immune functions. A gE-gI–bound IgG can participate in antibody bipolar bridging (ABB) such that the Fabs bind a viral antigen and the Fc binds gE-gI. The fate of ABB complexes had been unknown. This paper uses used live cell fluorescent imaging to follow ABB complexes during their formation and transport within a cell. ABB assemblies were internalized into acidic intracellular compartments, where gE-gI dissociated from IgG–viral antigen complexes and the IgG and antigen were targeted for degradation within lysosomes. These results suggest that gE-gI mediates clearance of infected cell surfaces of both anti-viral IgGs and viral antigens, a general mechanism to facilitate latent infection by evading IgG-mediated responses.

The Herpes Virus Fc Receptor gE-gI Mediates Antibody Bipolar Bridging to Clear Viral Antigens from the Cell Surface. (2014) PLoS Pathog 10(3): e1003961. doi:10.1371/journal.ppat.1003961