Herpes Virus Fusion and Entry: A Story with Many Characters. (2012) Viruses 4, 800-832; doi:10.3390/v4050800
Herpesviridae comprise a large family of enveloped DNA viruses all of whom employ orthologs of the same three glycoproteins, gB, gH and gL. Additionally, herpesviruses often employ accessory proteins to bind receptors and/or bind the heterodimer gH/gL or even to determine cell tropism. Sorting out how these proteins function has been resolved to a large extent by structural biology coupled with supporting biochemical and biologic evidence. Together with the G protein of vesicular stomatitis virus, gB is a charter member of the Class III fusion proteins. Unlike VSV G, gB only functions when partnered with gH/gL. However, gH/gL does not resemble any known viral fusion protein and there is evidence that its function is to upregulate the fusogenic activity of gB. In the case of herpes simplex virus, gH/gL itself is upregulated into an active state by the conformational change that occurs when gD, the receptor binding protein, binds one of its receptors. In this review we focus primarily on prototypes of the three subfamilies of herpesviruses. We will present our model for how herpes simplex virus (HSV) regulates fusion in series of highly regulated steps. Our model highlights what is known and also provides a framework to address mechanistic questions about fusion by HSV and herpesviruses in general.

Evaluation of invertebrate infection models for pathogenic corynebacteria. FEMS Immunol Med Microbiol. 22 Mar 2012. doi: 10.1111/j.1574-695X.2012.00963.x
For several pathogenic bacteria, model systems for host-pathogen interactions were developed, which provide the possibility of quick and cost-effective high throughput screening of mutant bacteria for genes involved in pathogenesis. A number of different model systems, including amoeba, nematodes, insects, and fish, have been introduced, and it was observed that different bacteria respond in different ways to putative surrogate hosts, and distinct model systems might be more or less suitable for a certain pathogen. The aim of this study was to develop a suitable invertebrate model for the human and animal pathogens Corynebacterium diphtheriae, Corynebacterium pseudotuberculosis, and Corynebacterium ulcerans. The results obtained in this study indicate that Acanthamoeba polyphaga is not optimal as surrogate host, while both Caenorhabtitis elegans and Galleria larvae seem to offer tractable models for rapid assessment of virulence between strains. Caenorhabtitis elegans gives more differentiated results and might be the best model system for pathogenic corynebacteria, given the tractability of bacteria and the range of mutant nematodes available to investigate the host response in combination with bacterial virulence. Nevertheless, Galleria will also be useful in respect to innate immune responses to pathogens because insects offer a more complex cell-based innate immune system compared with the simple innate immune system of C. elegans.

• Read the paper: A draft genome of Yersinia pestis from victims of the Black Death.
• Be on Twitter at 8pm UK time tonight.
• Join in the conversation via the hashtag: #microtwjc

Nice short review the current knowledge on five issues relevant to prion diseases:

• How do prions enter the body?
• How do prions reach the central nervous system?
• How do prions damage the CNS?
• Do mammals have an antiprion defense system?
• How can the prion problem be resolved for good?

Five Questions on Prion Diseases. (2012) PLoS Pathog 8(5): e1002651. doi:10.1371/journal.ppat.1002651

Richard Elliot from the University of St Andrews gives an update on the current situation with Schmallenberg virus, along with details on the virology of the virus, and some thoughts on prospects for vaccine development. This Hot Topic lecture was recorded on 27 March at the Society for General Microbiology’s Spring Conference 2012 in Dublin.

A new paper uses a dataset of rabies virus sequences collected from bat species throughout the Americas to test the role of inter-specific differences in reservoir host biology on the tempo of viral evolution. This shows the annual rate of molecular evolution to be a malleable trait of viruses that is accelerated in subtropical and tropical bats compared to temperate species. The association between geography and the speed of evolution appears to reflect differences in the seasonality of rabies virus transmission in different climatic zones.

These results illustrate that the viral mechanisms commonly invoked to explain heterogeneous rates of evolution among viral families may be insufficient to explain evolution in multi-host viruses and indicate a role for host biology in shaping the speed of viral evolution.

Rates of Viral Evolution Are Linked to Host Geography in Bat Rabies. (2012) PLoS Pathog 8(5):e1002720. doi:10.1371/journal.ppat.1002720
Rates of evolution span orders of magnitude among RNA viruses with important implications for viral transmission and emergence. Although the tempo of viral evolution is often ascribed to viral features such as mutation rates and transmission mode, these factors alone cannot explain variation among closely related viruses, where host biology might operate more strongly on viral evolution. Here, we analyzed sequence data from hundreds of rabies viruses collected from bats throughout the Americas to describe dramatic variation in the speed of rabies virus evolution when circulating in ecologically distinct reservoir species. Integration of ecological and genetic data through a comparative Bayesian analysis revealed that viral evolutionary rates were labile following historical jumps between bat species and nearly four times faster in tropical and subtropical bats compared to temperate species. The association between geography and viral evolution could not be explained by host metabolism, phylogeny or variable selection pressures, and instead appeared to be a consequence of reduced seasonality in bat activity and virus transmission associated with climate. Our results demonstrate a key role for host ecology in shaping the tempo of evolution in multi-host viruses and highlight the power of comparative phylogenetic methods to identify the host and environmental features that influence transmission dynamics.

Helicobacter pylori infection: what’s new. Current Opinion in Infectious Diseases, 25(3): 337–344
Helicobacter pylori colonizes the human stomach causing gastritis and severe diseases including gastric cancer. One of the most dangerous H. pylori factors, CagA, has been investigated in relation to gastric cancer: recently this relationship was strongly reinforced by the finding that CagA interacts with the tumor suppressor apoptosis-stimulating protein of p53-2 (ASPP2), promoting p53 degradation. Treg have been proposed to be involved in H. pylori infection and gastric disease: recent findings suggest that Treg-induced tolerance, rather than immunity to H. pylori, may result in less severe disease. The eradication rates achieved with the standard triple therapy dropped below 80%, mainly due to antibiotic resistance, while no vaccines are currently licensed; new treatments/regimens were subjected to clinical trials, in some cases strongly increasing the eradication rates.

Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology, 9 May 2012, doi:10.1016/S1470-2045(12)70137-7
Background: Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted.
Methods: We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data.
Findings: Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years.
Interpretation: Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide.

Julian Davies presents the SGM Prize Medal Lecture ‘Molecules, Microbes and Me’ on 26 March at the Society for General Microbiology’s Spring Conference 2012 in Dublin.