Posts Tagged ‘Emerging disease’
Bluetongue is a severe disease of ruminants, notably sheep and cattle. The causal agent, the dsRNA Bluetongue virus, is spread by an insect vector and occurs in its vector’s habitat in temperate climates throughout much of the world. BTV is the type member of genus Orbivirus in the family Reoviridae, with 26 known serotypes. When bluetongue first broke out in the United Kingdom in autumn of 2007, the disease was already rapidly spreading throughout continental Europe, causing high mortality rates in sheep and having a detrimental effect on the livestock trade through trade restrictions and loss of stock. The only effective weapon against the disease is control of the spread of BTV through rigorous vaccination programmes. Currently available commercial vaccines are based on both inactivated virus and live, attenuated strains and protect against a single serotype or multiple serotypes when provided as a cocktail. However, the possibility of recombination between the live vaccine strain(s) and wild-type virus in infected animals, leading to the emergence of new infectious strains has motivated efforts to develop safer vaccines.
One approach in the development of an inherently safe vaccine has been the production of Bluetongue virus-like particles (VLPs). BTV has a nonenveloped icosahedral structure, with four main structural proteins (VP3, VP7, VP5 and VP2) arranged in concentric shells around the segmented double-stranded RNA genome and minor structural and nonstructural proteins involved in virus replication. French et al. have shown that these four structural proteins, expressed in insect cells using a baculovirus expression system, assemble into virus-like particles devoid of nucleic acid.
This paper describes plant-based high-level expression of assembled subcore-, core- and virus-like particles of BTV serotype 8. Purified preparations of the VLPs, consisting of all four structural proteins, elicited an immune response in sheep and provided protective immunity against challenge with a South African BTV-8 field isolate. This demonstrates that plant expression provides an economically viable method for producing complex VLPs, such as those of BTV, with the desired biological properties. It represents a significant advance in the use of plant-based systems for the production of complex biopharmaceuticals. The methods employed could also be applied to other situations where the expression of multiple proteins is required, such as the reconstruction of metabolic pathways.
A method for rapid production of heteromultimeric protein complexes in plants: assembly of protective bluetongue virus-like particles. Plant Biotechnol J. 06 May 2013 doi: 10.1111/pbi.12076
Plant expression systems based on nonreplicating virus-based vectors can be used for the simultaneous expression of multiple genes within the same cell. They therefore have great potential for the production of heteromultimeric protein complexes. This work describes the efficient plant-based production and assembly of Bluetongue virus-like particles (VLPs), requiring the simultaneous expression of four distinct proteins in varying amounts. Such particles have the potential to serve as a safe and effective vaccine against Bluetongue virus (BTV), which causes high mortality rates in ruminants and thus has a severe effect on the livestock trade. Here, VLPs produced and assembled in Nicotiana benthamiana using the cowpea mosaic virus-based HyperTrans (CPMV-HT) and associated pEAQ plant transient expression vector system were shown to elicit a strong antibody response in sheep. Furthermore, they provided protective immunity against a challenge with a South African BTV-8 field isolate. The results show that transient expression can be used to produce immunologically relevant complex heteromultimeric structures in plants in a matter of days. The results have implications beyond the realm of veterinary vaccines and could be applied to the production of VLPs for human use or the coexpression of multiple enzymes for the manipulation of metabolic pathways.
1. Coronaviruses are a family of viruses that includes viruses that may cause a range of illnesses in humans, from common cold-type respiratory infections to SARS. Viruses of this family also cause a number of animal diseases.
2. What’s it called again?
Currently being referred to as nCoV or nCoV-2012, this virus has also been called Human Coronavirus-Erasmus Medical Center (hCoV-EMC), or Middle East respiratory syndrome coronavirus (MERS-CoV), and even “Saudi SARS” (it’s not – SARS is a related but different Coronavirus).
3. The first known case of nCoV infection was in a Saudi Arabian man who died in early 2012. This particular strain of coronavirus had not been previously identified in humans. The second confirmed case appeared in early September 2012, involving a 49-year old man in Doha, Qatar who had traveled to Saudi Arabia around the same time that the first case was identified. Currently, at least 40 cases have been confirmed, and 20 of those affected have died. The virus has also been found in Tunisia.
4. Where did it come from?
Bats. (It’s [nearly] always bats.) Bat coronaviruses carried by the genus Pipistrellus that differ from nCoV by as little as 1.8%. The existence of over 50 species of Pipistrellus bats in the Arabian Peninsula suggests that they may be the animal reservoir.
5. Symptoms of nCoV infection include renal failure and severe acute pneumonia, which often result in a fatal outcome. In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells because it uses dipeptidyl peptidase 4 (DPP4, also known as CD26) as a receptor.
6. nCoV can penetrate the bronchial epithelium and evade the innate immune system, signs that it is well-equipped for infecting human cells. This suggests that although nCoV may have jumped from animals to humans very recently, it is as well adapted to infecting the human respiratory tract as other, more familiar human coronaviruses, including the SARS virus and the common cold Coronavirus HCoV-229E.
7. The virus is susceptible to treatment with interferons, immune proteins that have been used successfully to treat other viral diseases, offering a possible method of treatment in the event of a large-scale outbreak.
8. How is it transmitted?
Almost certainly like other respiratory viruses, via aerosol droplets from coughs and sneezes, but possibly also by unwashed hands contaminated with respiratory secretions.
9. Is there a vaccine?
Not yet. It is possible to make vaccines agains Coronaviruses and several SARS vaccines were developed but never put into use because the SARS outbreak died away. It should be possible to make a nCoV vaccine if we need one.
10. Is there any travel advice?
At the moment the World Health Organization says there is no reason to impose any travel restrictions. Travel advice will be kept under review if additional cases occur or when the patterns of transmission become clearer.
11. Are we all going to die?
Probably not. Most of the people who have been infected so far have been older men, often with other medical conditions. The outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 infected over 8000 people and killed nearly 800 before burning itself out. But SARS didn’t kill us all and it’s unlikely that nCoV will either.
Other things you should know:
- 10 things you should know about H1N1 (swineflu)
- 10 things you should know about E. coli
- 10 things you didn’t know about Schmallenberg virus
- 10 things about Foot and Mouth Disease
The ongoing dance between a virus and its host shapes how the virus evolves. While human adenoviruses typically cause mild infections, recent reports have described newly characterized adenoviruses that cause severe, sometimes fatal human infections. A new paper describes a systems biology approach to show how evolution has affected the disease potential of a recently identified novel human adenovirus. A comprehensive understanding of virus evolution and pathogenicity is essential to our capacity to foretell the potential impact on human disease for new and emerging viruses.
Predicting the next eye pathogen: analysis of a novel adenovirus. (2013) MBio. 4(2): e00595-12. doi: 10.1128/mBio.00595-12
For DNA viruses, genetic recombination, addition, and deletion represent important evolutionary mechanisms. Since these genetic alterations can lead to new, possibly severe pathogens, we applied a systems biology approach to study the pathogenicity of a novel human adenovirus with a naturally occurring deletion of the canonical penton base Arg-Gly-Asp (RGD) loop, thought to be critical to cellular entry by adenoviruses. Bioinformatic analysis revealed a new highly recombinant species D human adenovirus (HAdV-D60). A synthesis of in silico and laboratory approaches revealed a potential ocular tropism for the new virus. In vivo, inflammation induced by the virus was dramatically greater than that by adenovirus type 37, a major eye pathogen, possibly due to a novel alternate ligand, Tyr-Gly-Asp (YGD), on the penton base protein. The combination of bioinformatics and laboratory simulation may have important applications in the prediction of tissue tropism for newly discovered and emerging viruses.
Smallpox may have been eradicated 35 years ago, but we are still battling many other major global health scourges. Malaria, for example, kills some 1.2 million people every year, and recent cholera epidemics in Zimbabwe, Somalia and Haiti have killed thousands. The death toll from HIV/AIDS is even higher, with almost 2 million deaths last year, but new drugs and health care delivery mechanisms mean that this number is falling.
But there’s one major disease where the battle is still being badly lost – tuberculosis. Mycobacterium tuberculosis still kills nearly 2 million people in the developing world every year. Even more alarmingly, in 2005 researchers in the province of KwaZulu-Natal in South Africa spotted an outbreak of a strain of M. tuberculosis that was resistant to the four key classes of drugs used to treat the disease. These super drug-resistant bugs have now been found in 58 countries, their spread fuelled by the lethal combination of HIV and TB. The mortality rate worldwide for the victims of this extensively drug resistant TB (XDR-TB) is more than 80%, making diagnosis almost a death sentence.
The scientific and medical challenges are huge. We don’t have an effective vaccine. We lack diagnostics and biomarkers. The current drug regimen – multiple drugs that must be taken reliably for six months – is virtually impossible to administer successfully in the developing world, where rural farmers may have to walk three hours to the nearest clinic. Too often, treatment simply leads to the development of drug resistance. And we have only just begun to study the bacterium’s biology and to learn how it manipulates the human immune system.
To understand TB and its deadly synergy with HIV, and to develop new diagnostics and treatments, we need more research. But the current research model could use some help. This article describes a new approach that involves bringing world-leading basic research to the epicenter of epidemics, rather than trying to fight diseases from laboratories at universities or government agencies thousands of miles away.
Virologists I’ve spoken to favor a phenomenon known as “viral chatter.” Viruses don’t just barge across the species barrier in one great rush. They tentatively make incursions–many of them spread across years. The SARS virus, for example, infected a few people before becoming a massive epidemic in 2003. During these incursions, animal viruses may acquire mutations that gradually prepare them to become good at spreading from person to person.
The Loom: http://goo.gl/mPmzq
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Since their discovery in 1971, the polyomaviruses JC (JCPyV) and BK (BKPyV), isolated from patients with progressive multifocal leukoencephalopathy and polyomavirus-associated nephropathy, respectively, remained for decades as the only known members of the Polyomaviridae family of viruses of human origin. Over the past five years, the application of new genomic amplification technologies has facilitated the discovery of several novel human polyomaviruses (HPyVs), bringing the present number to 10. These HPyVs share many fundamental features in common such as genome size and organization. Infection by all HPyVs is widespread in the human population, but they show important differences in their tissue tropism and association with disease. Much remains unknown about these new viruses.
This review discusses the problems associated with studying HPyVs, such as the lack of culture systems for the new viruses and the gaps in our basic understanding of their biology, and summarizes what is known so far about their distribution, life cycle, tissue tropism, their associated pathologies (if any), and future research directions.
The Rapidly Expanding Family of Human Polyomaviruses: Recent Developments in Understanding Their Life Cycle and Role in Human Pathology. (2013) PLoS Pathog 9(3): e1003206. doi:10.1371/journal.ppat.1003206
Until a few years ago the polyomavirus family (Polyomaviridae) included a dozen viruses identified in avian and mammal hosts. Two of these, the JC and BK-polyomaviruses isolated long time ago, are known to infect humans and cause severe illness in immunocompromized hosts. Since 2007 an unprecedented number of eight new polyomaviruses was discovered in humans. Among them are the KI and WU-polyomaviruses identified in respiratory samples, the Merkel cell polyomavirus found in skin carcinomas, and the polyomavirus associated with trichodysplasia spinulosa, a skin disease of transplant patients. Another four new human polyomaviruses were identified, HPyV6, HPyV7, HPyV9, and the Malawi polyomavirus, so far not associated with any disease. In the same period several new mammal polyomaviruses were described.
This review summarizes the recent developments in studying the new human polyomaviruses, and touches upon several aspects of polyomavirus virology, pathogenicity, epidemiology and phylogeny.
From Stockholm to Malawi: recent developments in studying human polyomaviruses. J Gen Virol. 19 Dec 2012
Novel Coronavirus is Well-adapted to Humans, Susceptible to Immunotherapy
The new coronavirus that has emerged in the Middle East is well-adapted to infecting humans but could potentially be treated with immunotherapy. HCoV-EMC can penetrate the bronchial epithelium and evade the innate immune system as easily as a cold virus can, signs that HCoV-EMC is well-equipped for infecting human cells. The study also reveals that the virus is susceptible to treatment with interferons, immune proteins that have been used successfully to treat other viral diseases, opening a possible mode of treatment in the event of a large-scale outbreak. http://goo.gl/kaUpj
2,016 confirmed cases of measles in England and Wales were reported to the Health Protection Agency (HPA) in 2012, the highest annual total since 1994. Dr Mary Ramsay, head of immunisation at the HPA, said: “Coverage of MMR is now at historically high levels but measles is highly infectious and can spread easily among communities that are poorly vaccinated, and can affect anyone who is susceptible, including toddlers in whom vaccination has been delayed. Older children who were not vaccinated at the routine age, who may now be teenagers, are at particular risk of becoming exposed, while at school for example. Measles continues to circulate in several European countries that are popular with holidaymakers. Measles is a highly infectious disease so the only way to prevent outbreaks is to make sure the UK has good uptake of the MMR vaccine, and that when cases are reported, immediate public health action is taken to target unvaccinated individuals in the vicinity as soon as possible.”
UK HPA: http://goo.gl/2Abgf
The Guardian: http://goo.gl/rnfRh