Detection of Rift Valley Fever Virus RNA in Formalin-Fixed Mosquitoes by In Situ Hybridization (RNAscope®).

Rift Valley fever virus (RVFV) causes a zoonotic mosquito-borne haemorrhagic disease that emerges to produce rapid large-scale outbreaks in livestock within sub-Saharan Africa. A range of mosquito species in Africa have been shown to transmit RVFV, and recent studies have assessed whether temperate mosquito species are also capable of transmission. In order to support vector competence studies, the ability to visualize virus localization in mosquito cells and tissue would enhance the understanding of the infection process within the mosquito body. Here, the application of in situ hybridization utilizing RNAscope® to detect RVFV infection within the mosquito species, Culex pipiens, derived from the United Kingdom was demonstrated. Extensive RVFV replication was detected in many tissues of the mosquito with the notable exception of the interior of ovarian follicles

Evidence of arbovirus co-infection in suspected febrile malaria and typhoid patients in Nigeria

Introduction: Clinical symptoms of malaria and typhoid infections are virtually indistinguishable from those initially seen in many arbovirus infections. Here we describe arbovirus co-infection detected in 310 sera samples collected from febrile, clinically suspected malaria/typhoid patients in Borno State, Nigeria. Methodology: Tested initially for Plasmodium falciparum by microscopy and for Salmonella Typhi by Widal test, samples were subsequently tested for chikungunya (CHIKV), yellow fever (YFV), dengue (DENV) and West Nile viruses (WNV) by plaque reduction neutralization test. Results: While 92% of patients tested positive for malaria, typhoid, an arbovirus infection, or a combination of one or more of these types of infections, less than 1% of the patients tested positive for malaria alone and only 3.9% tested positive for typhoid alone. Approximately half of the patients tested positive for infection with a single arbovirus (48%) regardless of the presence or absence of malaria or typhoid. Of those who showed 90% to 95% virus neutralization, 67.7% had neutralizing antibodies against DENV, 50% against CHIKV, 25% against WNV and 8.7% against YFV. Eight per cent tested negative against all six pathogens, suggesting that other arboviruses not tested for in this study may also be circulating in Nigeria. Conclusions: The results suggest that misdiagnosis of arbovirus co-infections as malaria infections, combined with a lack of virus surveillance and underreporting of arbovirus infections, increases the potential for undetected and uncontrolled spread of important vector-borne arboviruses becoming serious underlying public health concerns in Nigeria

A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus

Summary: The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally. : Allen et al. reveal a molecular basis of antibody-mediated neutralization of Rift Valley fever virus, an important human and animal pathogen. They isolate and demonstrate the protective efficacy of a monoclonal antibody in a murine model of virus infection, providing a blueprint for rational therapeutic and vaccine design. Keywords: phlebovirus, Rift Valley fever virus, antibody, structure, bunyavirus, virus-host interactions, immune response, vaccine, antiviral, neutralizatio

Orbital-selective Mott transitions: Heavy fermions and beyond

Quantum phase transitions in metals are often accompanied by violations of Fermi liquid behavior in the quantum critical regime. Particularly fascinating are transitions beyond the Landau-Ginzburg-Wilson concept of a local order parameter. The breakdown of the Kondo effect in heavy-fermion metals constitutes a prime example of such a transition. Here, the strongly correlated f electrons become localized and disappear from the Fermi surface, implying that the transition is equivalent to an orbital-selective Mott transition, as has been discussed for multi-band transition-metal oxides. In this article, available theoretical descriptions for orbital-selective Mott transitions will be reviewed, with an emphasis on conceptual aspects like the distinction between different low-temperature phases and the structure of the global phase diagram. Selected results for quantum critical properties will be listed as well. Finally, a brief overview is given on experiments which have been interpreted in terms of orbital-selective Mott physics.Comment: 29 pages, 4 figs, mini-review prepared for a special issue of JLT

History and classification of Aigai virus (formerly Crimean-Congo haemorrhagic fever virus genotype VI)

Crimean-Congo haemorrhagic fever virus (CCHFV) is the medically most important member of the rapidly expanding bunyaviral family Nairoviridae. Traditionally, CCHFV isolates have been assigned to six distinct genotypes. Here, the International Committee on Taxonomy of Viruses (ICTV) Nairoviridae Study Group outlines the reasons for the recent decision to re-classify genogroup VI (aka Europe-2 or AP-92-like) as a distinct virus, Aigai virus (AIGV)

UK vaccines network:Mapping priority pathogens of epidemic potential and vaccine pipeline developments

During the 2013–2016 Ebola outbreak in West Africa an expert panel was established on the instructions of the UK Prime Minister to identify priority pathogens for outbreak diseases that had the potential to cause future epidemics. A total of 13 priority pathogens were identified, which led to the prioritisation of spending in emerging diseases vaccine research and development from the UK. This meeting report summarises the process used to develop the UK pathogen priority list, compares it to lists generated by other organisations (World Health Organisation, National Institutes of Allergy and Infectious Diseases) and summarises clinical progress towards the development of vaccines against priority diseases. There is clear technical progress towards the development of vaccines. However, the availability of these vaccines will be dependent on sustained funding for clinical trials and the preparation of clinically acceptable manufactured material during inter-epidemic periods

ICTV Virus Taxonomy Profile: Nairoviridae.

Members of the family Nairoviridae produce enveloped virions with three single-stranded RNA segments comprising 17.1 to 22.8 kb in total. These viruses are maintained in arthropods and transmitted by ticks to mammals or birds. Crimean-Congo hemorrhagic fever virus is tick-borne and is endemic in most of Asia, Africa, Southern and Eastern Europe whereas Nairobi sheep disease virus, which is also tick-borne, causes lethal haemorrhagic gastroenteritis in small ruminants in Africa and India. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Nairoviridae, which is available at ictv.global/report/nairoviridae

Elucidation of the ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host-cell protein function

Viral pathogenesis in the infected cell is a balance between antiviral responses and subversion of host-cell processes. Many viral proteins specifically interact with host-cell proteins to promote virus biology. Understanding these interactions can lead to knowledge gains about infection and provide potential targets for antiviral therapy. One such virus is Ebola, which has profound consequences for human health and causes viral hemorrhagic fever where case fatality rates can approach 90%. The Ebola virus VP24 protein plays a critical role in the evasion of the host immune response and is likely to interact with multiple cellular proteins. To map these interactions and better understand the potential functions of VP24, label-free quantitative proteomics was used to identify cellular proteins that had a high probability of forming the VP24 cellular interactome. Several known interactions were confirmed, thus placing confidence in the technique, but new interactions were also discovered including one with ATP1A1, which is involved in osmoregulation and cell signaling. Disrupting the activity of ATP1A1 in Ebola-virus-infected cells with a small molecule inhibitor resulted in a decrease in progeny virus, thus illustrating how quantitative proteomics can be used to identify potential therapeutic targets

The Hubbard model within the equations of motion approach

The Hubbard model has a special role in Condensed Matter Theory as it is considered as the simplest Hamiltonian model one can write in order to describe anomalous physical properties of some class of real materials. Unfortunately, this model is not exactly solved except for some limits and therefore one should resort to analytical methods, like the Equations of Motion Approach, or to numerical techniques in order to attain a description of its relevant features in the whole range of physical parameters (interaction, filling and temperature). In this manuscript, the Composite Operator Method, which exploits the above mentioned analytical technique, is presented and systematically applied in order to get information about the behavior of all relevant properties of the model (local, thermodynamic, single- and two- particle ones) in comparison with many other analytical techniques, the above cited known limits and numerical simulations. Within this approach, the Hubbard model is shown to be also capable to describe some anomalous behaviors of the cuprate superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference