MicrobiologyBytes

The UK commercial poultry industry is an important industry to the British government, the consumer and farmers alike. Worth an estimated £3.4 billion at retail value, producing over 174 million birds for consumption per year, poultry diseases are of widespread interest, both from the point-of-view of understanding different poultry farming methods, and in terms of studying the potential impact of different diseases on poultry. However, our knowledge of how poultry farms in the UK are connected to each other by the movement of people and equipment is more limited. This is essential for effective prevention and control for potential outbreaks of diseases transmitted by the movement of people and equipment between farms within the commercial poultry industry. Diseases spread in such a way include avian influenza viruses (AIV), Newcastle disease virus, Salmonella and Campylobacter species.

An epidemic of any poultry disease with high mortality or which is zoonotic, such as AIV, would result in the culling of significant numbers of birds, as seen in the Netherlands in 2003 and Italy in 2000. Such an epidemic would cost the UK government millions of pounds in compensation costs, with further economic losses through reduction of international and UK consumption of British poultry. In order to better inform policy advisers and makers on the potential for a large epidemic in the UK, we investigate the role that interactions amongst premises within the British commercial poultry industry could play in promoting an AIV epidemic, given an introduction of the virus in a specific part of poultry industry in the UK.

Poultry premises using multiple slaughterhouses lead to a large number of premises being potentially connected, with the resultant potential for large and sometimes widespread epidemics. Catching companies can also potentially link a large proportion of the poultry population. Critical to this is the maximum distance traveled by catching companies between premises and whether or not between-species transmission could occur within individual premises. Premises closely linked by proximity may result in connections being formed between different species and or sectors within the industry.

Even quite well-contained epidemics have the potential for geographically widespread dissemination, potentially resulting in severe logistical problems for epidemic control, and with economic impact on a large part of the country. Premises sending birds to multiple slaughterhouses or housing multiple species may act as a bridge between otherwise separate sectors of the industry, resulting in the potential for large epidemics. Investment into further data collection and analyses on the importance of industry structure as a determinant for spread of AIV would enable us to use the results from this study to contribute to policy on disease control.

Contact structures in the poultry industry in Great Britain: Exploring transmission routes for a potential avian influenza virus epidemic. BMC Vet Res. 2008 4: 27

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• H5N1 influenza is no longer bird flu
• Negative sense RNA viruses
• Human Infections with Avian Influenza H5N1 Viruses
• Media coverage affects how people perceive the threat of disease

Popular media coverage of infectious diseases greatly influences how people perceive those diseases, making them seem more dangerous, according to a new study. The research suggests diseases that show up frequently in the print media are considered more serious than similar diseases that do not receive the same kind of coverage, such as yellow fever. Researchers chose ten infectious diseases drawn from the Centre for Disease Control database. Five were medical disorders that have been highly prevalent in the recent print media – anthrax, SARS, West Nile virus, Lyme disease and avian flu – and five were medical disorders that have not often been present in current media: Tularemia, human babesiosis, yellow fever, Lassa fever and hantavirus. Two groups of students, undergraduate and medical students, were asked to rate how serious, how prevalent, and how “disease-like” various conditions were.

A single incident reported in the media can cause great public concern if it is interpreted to mean that the potential risk is difficult to control, as with the possibility of a pandemic like in the case of avian flu, and bioterrorism, as in the case of anthrax infection. Conversely, when participants were presented with the descriptions of the disease, without the name, they actually thought that the diseases which received infrequent media coverage – the control group – were actually worse. Another interesting aspect of the study is when factual information about the diseases is presented along with the names, the media effect wasn’t nearly as strong. This suggests that people can overcome the influence of the media when you give them the facts, and so objective reporting is really critical. Equally surprising is the fact that the medical students – who should have more factual knowledge about these diseases – were just as influenced by the media, despite their background.

Medicine in the Popular Press: The Influence of the Media on Perceptions of Disease. 2008 PLoS ONE 3(10): e3552
In an age of increasing globalization and discussion of the possibility of global pandemics, increasing rates of reporting of these events may influence public perception of risk. The present studies investigate the impact of high levels of media reporting on the perceptions of disease. Undergraduate psychology and medical students were asked to rate the severity, future prevalence and disease status of both frequently reported diseases (e.g. avian flu) and infrequently reported diseases (e.g. yellow fever). Participants considered diseases that occur frequently in the media to be more serious, and have higher disease status than those that infrequently occur in the media, even when the low media frequency conditions were considered objectively ‘worse’ by a separate group of participants. Estimates of severity also positively correlated with popular print media frequency in both student populations. However, we also see that the concurrent presentation of objective information about the diseases can mitigate this effect. It is clear from these data that the media can bias our perceptions of disease.

On 12 September 2008, a tourist guide organising safari trips in Lusaka, Zambia, was evacuated in a critical condition to Johannesburg, South Africa. She was admitted to a clinic where she died on 14 September about 10 days after the onset of symptoms. The symptoms included a prodromal phase with fever, myalgia, vomiting, diarrhoea, followed by rash, liver dysfunction and convulsions. Cerebral oedema was detected on scan examination. No laboratory specimen was available for investigation. A total of four cases have now been reported.

On 12 October 2008, the National Institute for Communicable Diseases  in South Africa provided preliminary evidence that the causative agent of the disease was a virus from the Arenaviridae family. Specimens were shipped to the United States Centers for Disease Control and Prevention in Atlanta for additional investigations.

Arenaviruses are enveloped viruses (about 120 nm diameter) with a bi-segmented negative strand RNA genome. The typical image in electronic microscopy showing grainy ribosomal particles (from arena, the Latin for “sand”) inside the virions gave the name to this family of viruses. The prototype is the Lymphocytic Choriomeningitis (LCM) virus (LCMV), isolated in 1933 in North America from a human case with aseptic meningitis. Cases caused by LCMV occur worldwide. Other arenaviruses causing hemorrhagic fevers were reported in South America, causing sporadic cases or limited outbreaks: Junín virus in 1958 in Argentina, Machupo virus in 1963 in Bolivia, Guanarito virus in 1990-1991 in Venezuela, Sabia virus in 1990 in Brazil and more recently Chapare virus in 2004 in Bolivia. In West Africa, Lassa virus was identified in Nigeria in 1969. It causes thousands of cases each year in Sierra Leone, Liberia, Guinea and Nigeria. However, only limited data are available to assess the real incidence of Lassa fever in Africa.

Unknown disease in South Africa identified as arenavirus infection. Euro Surveill. 2008;13(42):pii=19008

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• A new arenavirus associated with hemorrhagic fever
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Patients who succumbed to influenza during the 1918 pandemic had severe lung pathology marked by extensive inflammatory infiltrate, indicating a robust immune response in the lung. Similar findings have been reported from H5N1-infected patients, raising the question as to why people expire in the presence of a strong immune response. A new paper addresses this question by characterizing the immune cell populations in the mouse lung following infection with the 1918 pandemic virus and two H5N1 viruses isolated from fatal cases. The data shows excessive immune cell infiltration in the lungs contributing to severe consolidation and tissue architecture destruction in mice infected with highly pathogenic influenza viruses, supporting the histopathological observations of lung tissue from 1918 and H5N1 fatalities. The researchers found that certain cells of the innate immune system, specifically macrophages and neutrophils, increase significantly into the mouse lung shortly following HP virus infection. Interestingly, lung macrophages and dendritic cells were shown to be susceptible to 1918 and H5N1 virus infection in vitro or ex vivo, suggesting a possible mechanism of immunopathogenesis. Identification of the precise inflammatory cells associated with lung inflammation will be important for the development of treatments that could potentially enhance or modulate host innate immune responses. While reducing virus load through anti-viral intervention remains the best treatment option for H5N1 patients, therapies that moderate immunopathology may help to reduce the high case fatality rate currently associated with this virus infection.

H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice. PLoS Pathogens, 4 (8)
Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate. Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses. Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition and cellular immune temporal dynamics. Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections. These results together show that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection. In addition, primary macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro and in infected mouse lung tissue.

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• The Biology of Influenza
• Cellular Proteins in Influenza Virus Particles
• Influenza vaccines from plants

A new study portrays a comprehensive genome-scale map of human proteins and cellular pathways affecting the outcome of flavivirus–host cell interactions, and presents a potentially useful resource for further studies. These results may provide insights into the molecular differences in the pathogenesis of related flaviviruses, and reveal potential flavivirus therapeutic targets.

RNA interference screen for human genes associated with West Nile virus infection. Nature 455: 242-245
West Nile virus (WNV), and related flaviviruses such as tick-borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem. However, our understanding of the molecular interaction of such flaviviruses with mammalian host cells is limited. WNV encodes only 10 proteins, implying that it may use many cellular proteins for infection. WNV enters the cytoplasm through pH-dependent endocytosis, undergoes cycles of translation and replication, assembles progeny virions in association with endoplasmic reticulum, and exits along the secretory pathway. RNA interference (RNAi) presents a powerful forward genetics approach to dissect virus–host cell interactions. Here we report the identification of 305 host proteins that affect WNV infection, using a human-genome-wide RNAi screen. Functional clustering of the genes revealed a complex dependence of this virus on host cell physiology, requiring a wide variety of molecules and cellular pathways for successful infection. We further demonstrate a requirement for the ubiquitin ligase CBLL1 in WNV internalization, a post-entry role for the endoplasmic-reticulum-associated degradation pathway in viral infection, and the monocarboxylic acid transporter MCT4 as a viral replication resistance factor. By extending this study to dengue virus, we show that flaviviruses have both overlapping and unique interaction strategies with host cells. This study provides a comprehensive molecular portrait of WNV–human cell interactions that forms a model for understanding single plus-stranded RNA virus infection, and reveals potential antiviral targets.

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• West Nile Virus Pathogenesis
• Pathogenic Flaviviruses
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Researchers from the United States Department of Agriculture have identified a novel mutation in the bovine prion protein gene in a cow confirmed with atypical Bovine Spongiform Encephalopathy (BSE). This is the first report of a confirmed case of BSE (aka mad cow disease) with a potential pathogenic mutation within the bovine Prnp gene. BSE, a transmissible spongiform encephalopathy (TSE) or prion disease of cattle, was first discovered in the United Kingdom in 1986. BSE is considered to be the cause of a human prion disease known as variant Creutzfeldt-Jakob Disease (vCJD). Veterinary scientists have now identified a novel mutation, E211K, in the bovine Prnp gene. This mutation is identical to the E200K pathogenic mutation in the human Prnp, which has been described as the most common cause of genetic CJD. The study supports the view that all three etiological forms of TSEs in humans are also present in cattle: infectious, sporadic, and genetic. It further supports the hypothesis that the BSE epidemic may have originated from a genetic case of cattle BSE. Cattle with similar mutations can be expected in cattle herds world-wide and could be the source of new BSE outbreaks. It is therefore critical to continue world-wide surveillance for typical and atypical BSE cases including sequencing of the Prnp gene. A newly developed assay system for detecting the E211K mutation has been developed for this purpose. Finally, in order to protect humans it is essential to continue to exclude Specified Risk Materials from the food chain and to maintain the ruminant feed ban.

BSE Case Associated with Prion Protein Gene Mutation. PLoS Pathog 4(9): e1000156
Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle and was first detected in 1986 in the United Kingdom. It is the most likely cause of variant Creutzfeldt-Jakob disease (CJD) in humans. The origin of BSE remains an enigma. Here we report an H-type BSE case associated with the novel mutation E211K within the prion protein gene (Prnp). Sequence analysis revealed that the animal with H-type BSE was heterozygous at Prnp nucleotides 631 through 633. An identical pathogenic mutation at the homologous codon position (E200K) in the human Prnp has been described as the most common cause of genetic CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. A recent epidemiological study revealed that the K211 allele was not detected in 6062 cattle from commercial beef processing plants and 42 cattle breeds, indicating an extremely low prevalence of the E211K variant (less than 1 in 2000) in cattle. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in the approximately 10-year-old cow carrying the E221K mutation.

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• A novel approach in the molecular differentiation of prion strains
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CATS and dogs can carry the deadly bat-borne Hendra virus, a CSIRO scientist has revealed. Bruce Mungall, a research scientist at the CSIRO’s Australian Animal Health Laboratory in Geelong, said cats were “very susceptible” to the virus that killed Brisbane vet Ben Cunneen.
“They’re what we would call a dead-end host because if a cat becomes infected, there’s a good chance it would die,” he said yesterday.
“Dogs are a possibility as well. Nothing can be ruled in or out at this stage.”
Queensland’s chief vet, Ron Glanville, has told The Australian a cat at the veterinary stables where Dr Cunneen worked had tested negative to the virus last month. Yesterday, he ruled out a cull of fruit bats to prevent further outbreaks of Hendra virus. Bats were a protected species and an important part of the ecosystem.
“Bats are the natural reservoir of Hendra virus, there’s no doubt about it,” he said. “But it doesn’t make sense to control the population because they are so widespread. What we really need to do is develop strategies to prevent the virus spreading from bats to horses.”

Dogs and cats can carry Hendra virus, CSIRO

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• Hendra Virus

UK escapes the worst of bluetongue

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• Bluetongue virus
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The origin of the transmissible agent involved in the foodborne epidemic of bovine spongiform encephalopathy (BSE) remains a mystery. It has recently been proposed that this could have been the result of the recycling of an atypical, more probably sporadic, form of BSE (called bovine amyloidotic spongiform encephalopathy, or L-type BSE) in an intermediate host, such as sheep. A team from the French Food Safety Agency has identified a prion protein characteristic that is unique to some natural but unusual sheep scrapie cases. This finding may provide a novel method by which to study prion diversity and their possible changes during cross-species transmission. Mystery still surrounds the origin of the transmissible agent involved in the food-borne epidemic of bovine spongiform encephalopathy (BSE). Classical BSE, more commonly known as mad cow disease, is a known cause of a variant form of the incurable, degenerative neurological disorder Creutzfeldt-Jakob disease in humans. It has recently been proposed that this could have been the result of the recycling of an atypical, more probably sporadic form of BSE (called bovine amyloidotic spongiform encephalopathy, or L-type BSE) in an intermediate host, such as sheep. The team analyzed the molecular features of the disease-associated protease-resistant prion protein (PrPres) to determine any differences which might discriminate between scrapie and BSE cases. The researchers sampled PrPres from the brains of transgenic mice overexpressing the ovine prion protein after experimental infection with prions from bovine classical BSE, L-type BSE, and ovine scrapie. Scrapie cases were found to include rare “CH1641-Like” isolates, which share some PrPres molecular features with classical BSE and L-type BSE. The molecular features of the prion protein in the “CH1641-like” sheep scrapie cases more closely resemble those found in L-type BSE compared to classical BSE. However, from a series of four “CH1641-like” scrapie cases, the researchers found a pathological C-terminal prion protein product that was undetectable from both L-type and classical BSE transmitted to such mice, clearly suggesting that such scrapie isolates are not linked to these BSE forms. Further studies to confirm this discriminating factor are needed in sheep, especially from sheep experimentally infected with L-type BSE, which were not available for this study. These findings add a novel approach for the discrimination of prions that may help to understand their possible changes during cross-species transmissions.

A C-Terminal Protease-Resistant Prion Fragment Distinguishes Ovine “CH1641-Like” Scrapie from Bovine Classical and L-Type BSE in Ovine Transgenic Mice. 2008 PLoS Pathog 4(8): e1000137
The protease-resistant prion protein (PrPres) of a few natural scrapie isolates identified in sheep, reminiscent of the experimental isolate CH1641 derived from a British natural scrapie case, showed partial molecular similarities to ovine bovine spongiform encephalopathy (BSE). Recent discovery of an atypical form of BSE in cattle, L-type BSE or BASE, suggests that also this form of BSE might have been transmitted to sheep. We studied by Western blot the molecular features of PrPres in four “CH1641-like” natural scrapie isolates after transmission in an ovine transgenic model (TgOvPrP4), to see if “CH1641-like” isolates might be linked to L-type BSE. We found less diglycosylated PrPres than in classical BSE, but similar glycoform proportions and apparent molecular masses of the usual PrPres form (PrPres #1) to L-type BSE. However, the “CH1641-like” isolates differed from both L-type and classical BSE by an abundant, C-terminally cleaved PrPres product (PrPres #2) specifically recognised by a C-terminal antibody (SAF84). Differential immunoprecipitation of PrPres #1 and PrPres #2 resulted in enrichment in PrPres #2, and demonstrated the presence of mono- and diglycosylated PrPres products. PrPres #2 could not be obtained from several experimental scrapie sources (SSBP1, 79A, Chandler, C506M3) in TgOvPrP4 mice, but was identified in the 87V scrapie strain and, in lower and variable proportions, in 5 of 5 natural scrapie isolates with different molecular features to CH1641. PrPres #2 identification provides an additional method for the molecular discrimination of prion strains, and demonstrates differences between “CH1641-like” ovine scrapie and bovine L-type BSE transmitted in an ovine transgenic mouse model.

Related:

• New forms of bovine spongiform encephalopathy
• Four separate types of Creutzfeldt-Jakob disease?
• Genes contributing to prion pathogenesis
• What the heck are prions for?