Carrageenan Is a Potent Inhibitor of Papillomavirus Infection
Sexually transmitted human papillomavirus (HPV) infections are very common. Although most HPV infections don’t cause noticeable symptoms, persistent infection with some genital HPV types can lead to cervical cancer or other anal/genital cancers. Another subset of HPV types can cause genital warts. Recent studies have suggested that condoms are not highly effective in preventing HPV infection. Although HPV vaccines will soon become available, they probably will not protect against all genital HPV types and will be too expensive for use in the developing world. Inexpensive HPV-inhibitory compounds (known as topical microbicides) might be useful for blocking the spread of HPV. Using a newly developed cell culture–based HPV inhibition test, we have discovered that an inexpensive gelling agent called carrageenan is an unexpectedly potent HPV infection inhibitor. Carrageenan is also under investigation as a topical microbicide targeting HIV and herpes viruses, but it is a thousand times more effective against HPV in cell culture tests. Interestingly, carrageenan is used as a thickener in some commercially available sexual lubricants and lubricated condoms. Several of these commercial lubricant products are potent HPV inhibitors in our cell culture–infection system. Clinical trials are needed to determine the effectiveness of carrageenan as a topical microbicide against HPV.
Modulation of Tumor Necrosis Factor by Microbial Pathogens
In response to invasion by microbial pathogens, host defense mechanisms get activated by both the innate and adaptive arms of the immune responses. TNF (tumor necrosis factor) is a potent proinflammatory cytokine expressed by activated macrophages and lymphocytes that induces diverse cellular responses that can vary from apoptosis to the expression of genes involved in both early inflammatory and acquired immune responses. A wide spectrum of microbes has acquired elegant mechanisms to overcome or deflect the host responses mediated by TNF. For example, modulatory proteins encoded by multiple families of viruses can block TNF and TNF-mediated responses at multiple levels, such as the inhibition of the TNF ligand or its receptors, or by modulating key transduction molecules of the TNF signaling pathway. Bacteria, on the other hand, tend to modify TNF-mediated responses specifically by regulating components of the TNF signaling pathway. Investigation of these diverse strategies employed by viral and bacterial pathogens has significantly advanced our understanding of both host TNF responses and microbial pathogenesis. This review summarizes the diverse microbial strategies to regulate TNF and how such insights into TNF modulation could benefit the treatment of inflammatory or autoimmune diseases.
Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant
Prostate cancer is the most frequent cancer and the second leading cause of cancer deaths in US men over the age of 50. Several genetic factors have been proposed as potential risk factors for the development of prostate cancer, including a viral defense gene called RNASEL. A common genetic variant in this gene, R462Q, was recently implicated in up to 13% of prostate cancer cases. Given the antiviral role of RNASEL, the authors sought to examine if a virus might be present in prostate cancers associated with the R462Q variant. Using a DNA microarray designed to detect all known viral families, the authors identified a novel virus, named XMRV, in a subset of prostate tumor samples. Polymerase chain reaction testing of 86 prostate tumors for the presence of XMRV revealed a strong association between the presence of the virus and being homozygous for the R462Q variant. Cloning and sequencing of the virus showed that XMRV is a close relative of several known xenotropic murine leukemia viruses. This report presents the first documented cases of human infection with a xenotropic retrovirus. Future work will address the potential connection between XMRV infection and the increased prostate cancer risk in patients with the R462Q RNASEL variant.
Human Neutrophils Kill Bacillus anthracis Bacillus anthracis is the bacterium that causes anthrax, a disease that can occur through natural infections and also through intentional release. B. anthracis makes spores, which are in a dormant state, similar to seeds of a plant, and are extremely resistant to the environment. B. anthracis spores can infect through the skin or the lung. Lung infections disseminate through the body and are lethal. In contrast, skin infections often remain localized, and patients survive even without treatment. It is not well understood why these bacteria cause a localized infection through the skin and a lethal disease through the lung. Little is known about how B. anthracis is controlled. Neutrophils are the first white blood cells recruited to a site of infection and are specialized in killing microbes. Previous studies show that neutrophils are abundant in the skin form, but not in the lung form of anthrax. The researchers report that human neutrophils can take up B. anthracis spores. Once inside, the spores germinate to form vegetative bacteria. The vegetative bacteria are extremely susceptible to neutrophil-killing mechanisms. The B. anthracis virulence factors (molecules that make bacteria cause diseases) manipulate other human cells but do not deter neutrophils. B. anthracis is indeed exquisitely sensitive to the neutrophil protein α-defensin. These data support a new model where B. anthracis skin, but not lung, infections are controlled by the antimicrobial activity of neutrophils.
A Novel Bacterium Associated with Lymphadenitis in a Patient with Chronic Granulomatous Disease
As new bacteria continue to be discovered every year, it is inevitable that some of them will be found to cause human disease. The authors describe the isolation and characterization of a new bacterium, grown from a patient with chronic granulomatous disease (CGD). In this genetic disease, one of the main lines of defense against infection, the neutrophil, has a discrete defect in the generation of superoxide, leading to recurrent infections with a narrow spectrum of bacteria and fungi. This new organism was cultured from lymph nodes that had been inflamed for several months. To prove that this new bacterium was indeed a pathogen, Greenberg and colleagues measured specific antibody response in the patient: they inoculated CGD mice with this organism and reproduced the appearance of the human infection; they recovered the organism in pure growth from infected mouse spleens. This new bacterium belongs to the family Acetobacteraceae, bacteria that are found widely in the environment. They have a variety of industrial uses, such as the production of vinegar, but have never been reported to cause invasive human disease. Disease-causing organisms remain to be discovered. The researchers outline some of the steps that can be taken to verify the pathogenicity of novel organisms.
Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
Ebola virus (EBOV) causes a highly lethal hemorrhagic fever that results in up to 50%–90% mortality in humans. There are currently no available vaccines or therapeutics to treat EBOV infection. To date, multiple pre- and post-exposure therapeutic strategies, primarily focused on bolstering the host immune response or inhibiting viral replication, have been undertaken with limited success. Here, Bavari and colleagues report the development of a successful therapeutic regimen for EBOV infection based on antisense phosphorodiamidate morpholino oligomers (PMOs). PMOs are a subclass of chemically modified antisense oligonucleotides that interfere with the translation of viral mRNA, thus inhibiting viral amplification. Using a cell-free translation system, a cell-based assay, and survival studies in rodents, we identified several efficacious EBOV-specific PMOs. Further, prophylactic administration of a combination of three EBOV-specific PMOs specifically targeting VP24, VP35, and the viral polymerase L protected rhesus macaques from lethal EBOV infection. This is the first successful antiviral intervention against filoviruses in nonhuman primates. These findings may serve as the basis for a new strategy to quickly develop virus-specific therapies in defense against known, emerging, and genetically engineered bioterrorism threats.
The Role of Innate Immune Responses in the Outcome of Interspecies Competition for Colonization of Mucosal Surfaces
Bacterial infection commonly begins with organisms that colonize and proliferate on mucosal surfaces. These microenvironments may be occupied by multiple microbial species, suggesting that successful colonizers are distinguished by their capacity to prevail over their competitors. This study examines interactions between two bacterial species that both colonize and infect the human upper respiratory tract. In a mouse model, strains of both Haemophilus influenzae and Streptococcus pneumoniae efficiently colonize the nasal mucosa when tested individually. In contrast, following co-inoculation, H. influenzae rapidly and completely outcompetes S. pneumoniae. This competitive effect is dependent on the local responses from the host in the form of a specific type of white blood cell (neutrophil) that acts to engulf and kill microorganisms that have been labeled by proteins that bind to microbial surfaces (complement). The results of this study show that recognition of microbial products from one species may activate inflammatory responses that promote the clearance of another competing species. This study also demonstrates how manipulations such as antibiotics or vaccines, which are meant to diminish the presence of a single pathogen, may inadvertently alter the competitive interactions of complex microbial communities.
Prions Adhere to Soil Minerals and Remain Infectious
Transmissible spongiform encephalopathies (TSEs) are a group of incurable diseases likely caused by a misfolded form of the prion protein (PrPSc). TSEs include scrapie in sheep, bovine spongiform encephalopathy (“mad cow” disease) in cattle, chronic wasting disease (CWD) in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and CWD are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity, because PrPSc likely enters soil environments through urinary or alimentary shedding and decomposition of infected animals. In this manuscript, the authors test the potential for soil to serve as a reservoir for PrPSc and TSE infectivity. They demonstrate that PrPSc binds to a variety of soil minerals and to whole soils. They also quantitate the levels of protein binding to three common soil minerals and show that the interaction of PrPSc with montmorillonite, a common clay mineral, is remarkably strong. PrPSc bound to Mte remained infectious to laboratory animals, suggesting that soil can serve as a reservoir of TSE infectivity.
The Expanding Universe of Prion Diseases
Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrPC. Several mammalian species are affected by the diseases, and in the case of “mad cow disease” (BSE) the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases—including human diseases variant Creutzfeldt-Jakob disease (vCJD) and sporadic fatal insomnia (sFI), bovine amyloidotic spongiform encephalopathy (BASE), and Nor98 of sheep—have been identified in the last ten years, and chronic wasting disease (CWD) of North American deer (Odocoileus Specis) and Rocky Mountain elk (Cervus elaphus nelsoni) is undergoing a dramatic spread across North America. While amplification (BSE) and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk) can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of “sporadic” disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.
Crossing the Line: Selection and Evolution of Virulence Traits
The evolution of pathogens presents a paradox. Pathogenic species are often absolutely dependent on their host species for their propagation through evolutionary time, yet the pathogenic lifestyle requires that the host be damaged during this dependence. It is clear that pathogenic strategies are successful in evolutionary terms because a diverse array of pathogens exists in nature. Pathogens also evolve using a broad range of molecular mechanisms to acquire and modulate existing virulence traits in order to achieve this success. Detailing the benefit of enhanced selection derived through virulence and understanding the mechanisms through which virulence evolves are important to understanding the natural world and both have implications for human health.
Nice work. Open access publishing has come of age.
Canadian scientists seem to have proved the existence of a second mammalian prion protein. The original cellular prion protein, PrP(C), is neuroprotective in a number of settings. Shadoo (Sho) is a protein found in normal mouse brains which has homology to the N-terminus of PrP. Prion-infected mice exhibit a dramatic reduction in endogenous Sho protein, indicating that there is a relationship between PrP(C) and Sho, and that Sho appears to protect brain cells from harm, so reduced levels in prion infections may exacerbate brain damage. Sho may prove useful in deciphering many unresolved aspects of prion biology.
The term ‘prion’ means an infectious protein that does not need an accompanying nucleic acid. There are six known prions of fungi, including four self-propagating amyloids and two enzymes that are necessary to activate their inactive precursors:
[URE3] is a prion of the nitrogen catabolism regulator Ure2p
[PSI+] is a prion of the translation-termination factor Sup35p, which has a parallel beta-sheet structure.
[PIN+] is a prion of Rnq1p (function unknown)
[Het-s] is a prion of the heterokaryon incompatibility protein HETs; this prion of apparently benefits its host (Podospora anserina), whereas the [URE3] and [PSI+] prions of Saccharomyces cerevisiae are detrimental.
[β] is a prion of vacuolar protease B
[C] is a prion of a mitogen-activated protein kinase kinase kinase
This review explores the scope of the prion phenomenon, the biological and evolutionary roles of prions, the structural basis of the amyloid prions and the prominent role of chaperones (proteins that affect the folding of other proteins) and other cellular components in prion generation and propagation. Chaperones catalyse amyloid filament breakage to form new seeds, and probably have other roles in prion propagation and generation as well. Different prion variants, with the same protein sequence, have different amyloid structures. Variants can determine host range and chaperone effects.
Low numbers of cattle with abnormal prion proteins (PrPsc) with different biochemical properties from those normally associated with BSE have been detected in active surveillance programmes in a number of countries. Different forms of BSE were initially identified and distinguished from classical BSE on the basis of their PrPsc profiles in biochemical tests. All BSE cases identified to date conform to one of three different PrPsc profiles on western blot tests. The European Union (EU) Community Reference Laboratory has suggested that cases be classified on the basis of these profiles as classical, L- or H-type BSE. The key distinguishing features in western blot tests are the lower concentration of the diglycosylated band and the slightly lower molecular mass of unglycosylated band of PrPsc in L-type BSE, and the higher molecular mass of the unglycosylated band in H-type BSE, compared with classical BSE. A western blot method to discriminate between the three types of BSE has been developed.
A significant distinction between classical BSE and L- and H-type BSEs is the age distribution of cases as L- and H-type BSE are found in older cattle with an age range of 5.5 to 19 years. One putative L-type BSE case was aged two years, however the BSE typing of this case has not been verified. Around 85% of L- or H-type BSE cases have been found in animals more than 10 years old, which is much older than most cases of classical BSE. Neuropathological investigations suggest that PrPsc may be more widely distributed, with a different brain distribution pattern for L- and H-type BSE, compared with classical BSE. It is not possible to accurately quantify the number of H- or L-type BSE cases that have occurred world-wide. Information presented to SEAC indicated that at least 37 cases of L- and H-type BSE have been identified world-wide to date. These cases are widely distributed geographically with L-type cases identified in a number of European countries and Japan, and H-type cases identified in a number of European countries and North America.
It is not known whether L- or H-type BSE are newly emerging forms of BSE or whether they have existed for some time and have only come to light following extensive active surveillance programmes in the EU and elsewhere, together with the introduction and development of new biochemical tests. Genetic analyses of a few L- and H-type BSE cases have not identified associations between the occurrence of such cases and known genetic polymorphisms in the prion protein gene. There are no mutations in the prion protein gene open reading frame in all, but one, sequenced case. However, the analyses conducted to date are limited by the small number of cases and controls analysed. Thus, a genetic cause of the disease cannot be ruled out.
Transmission studies have demonstrated that both L- and H-type BSE are transmissible to other species by the intracerebral route. No studies have assessed the transmissibility by the oral route. Thus, the available information shows that it is possible for species other than cattle to develop these diseases upon infection. L-type BSE has been transmitted to wild-type, bovinised, ovinised and humanised mice as well as to cattle and a cynomolgus macaque by intracerebral inoculation. Incubation periods, clinical signs, neuropathology as well as the neurological distribution of PrPsc were distinct from classical BSE. With the exception of transmissions to wild-type mice, primary transmissions resulted in clinical disease. Although primary transmission to wild-type mice did not result in clinical disease, secondary transmissions from some of these animals resulted in clinical disease. Sub-passage of L-type BSE in wild-type and ovinised mice suggests that L-type BSE may be converted to an infection of a similar phenotype to classical BSE.
There are too few data to enable an assessment of the natural transmissibility of L- and H-type BSE between cattle, or to sheep or goats. The present feed control measures which prevent feeding of mammalian meat and bone meal to ruminants would limit the spread of these forms of BSE to cattle, sheep and goats should they be transmissible to these species by the oral route. Similarly, the lack of data on the oral transmissibility of L- or H-type BSE to humanised mice or non-human primates does not allow an assessment of the human health implications of ingestion of meat from animals infected with L- or H-type BSE. The differing clinical features of L-type and classical BSE in the cynomolgus macaque suggest that if L-type BSE were ever to be transmitted to humans, its clinical presentation may differ from that of vCJD. It is possible, therefore, that, if transmitted to humans, it could be identified by continuing surveillance of unusual neurological conditions in place in the UK.
Industrialized societies are in the middle of an epidemic in which the killers of youth are being replaced by the killers of old age. Among the most disturbing of these new threats are a set of degenerative brain diseases known as the amyloidoses. A number of different conditions are characterized by strange protein deposits in various organs of the body. These abnormal or “amyloid” deposits consist of accumulations of many different proteins in the form of spherical plaques or thin fibrils, depending on their origin. Scientists and doctors do not understand exactly how and why proteins become locked up in these deposits, except that the normal mechanisms which keep vigorous, healthy cells free of this accumulated junk must somehow become damaged or blocked.
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The underlying pathology in Alzheimer’s disease is caused by the presence of extracellular senile plaques and intracellular tangles within the brains of affected people. The major component of these structures are amyloid peptides, which are derived from the proteolytic processing of the amyloid precursor protein (APP).
More than 5 million Americans are estimated to have Alzheimer’s disease, and it was the 7th leading cause of death in the USA in 2004 with nearly 66,000 diagnosed deaths. It is predicted that 14.3 million Americans will have the disease by the middle of this century. In the UK, Alzheimer’s disease affects over 400,000 people and the number of diagnoses is growing year by year.
If you’re a regular reader of MicrobiologyBytes, you may know that the prion protein (PrP) is the causative agent of the transmissible spongiform encephalopathies (TSEs). These include Creutzfeldt–Jakob disease (CJD) and other conditions in humans, bovine spongiform encephalopathy (BSE or mad cow disease) in cattle, and scrapie in sheep. In these so-called prion diseases, the normal cellular form of PrP (PrPc) undergoes a conformational change to the infectious form of the protein, PrPSc. In spite of extensive studies, the normal cellular function of PrPc remains unknown, but it has been proposed to have various roles in metal homeostasis, neuroprotective signaling, and the cellular response to oxidative stress. Interestingly, Alzheimer’s disease and CJD share a variety of neuropathological features, and the Val/Met polymorphism at residue 129 in the gene encoding PrPc has been identified as a risk factor for the early onset of Alzheimer’s disease.
A recent paper in PNAS investigated whether PrPc alters the proteolytic processing of APP and so might lead to the formation of amyloid plaques (Cellular prion protein regulates beta-secretase cleavage of the Alzheimer’s amyloid precursor protein.
PNAS USA 2007 104: 11062-11067). Over expression of PrPc inhibited cleavage of APP and reduced amyloid formation. Conversely, depletion of PrPc in mouse cells by siRNA led to an increase in amyloid peptides secreted into the medium. In the brains of PrP knockout mice and in brains from scrapie-infected mice, amyloid levels were also significantly increased. Using constructs which expressed PrP, the researchers demonstrated that the regulatory effect of PrPc on the cleavage of APP required the localization of PrPc to cholesterol-rich lipid rafts in cell membranes.
The authors suggest it is conceivable that small changes in PrPc levels in individuals may affect proteolytic processing of APP in a subtle way over many decades to affect long-term amyloid production, which in turn could either accelerate or decelerate the deposition of amyloid in the brain. Whether this function is lost as a result of the normal ageing process, or if some people are more susceptible than others is not yet known.
In spite of their biochemical similarities, this is the first time a definite link has been made between PrP and Alzheimer’s disease. Ultimately, this could provide the foundations for novel approaches to finding new therapeutic targets in Alzheimer’s. But while this represents an advance in understanding Alzheimer’s disease, these observations also raise significant questions over whether depletion of PrPc is a sound therapeutic approach for prion diseases.
Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases of sheep, deer, and elk. Transmissible spongiform encephalopathies (TSEs) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (mad cow disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity and to bind the infectious agent.
TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of montmorillonite and soil-bound prions. We establish that prions bound to montmorillonite are orally bioavailable, and that, unexpectedly, binding to montmorillonite significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Oral exposure to montmorillonite-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent.
We’re getting fatter. The World Health Organization recently declared that there is an epidemic of obesity (having too much body fat). In the past 20 years, the prevalence of obesity has increased by 30% in the USA. In the UK it is estimated that one in five men and a quarter of women are obese and that as many as 30,000 people die prematurely every year from obesity-related conditions. Experts believe that obesity is responsible for even more ill health than smoking. Being significantly overweight is linked to a wide range of health problems, including: heart disease, high blood pressure, arthritis, diabetes, gallstones, some cancers (e.g. breast, prostate), stress, anxiety, and depression. Wouldn’t it be nice if it wasn’t all our fault, and if meaning to go to the gym was as effective as a long workout. Wouldn’t if be nice to have an excuse for being slightly tubby. In the last two decades, 10 adipogenic (fat causing) pathogens have been reported: these include human and nonhuman viruses, prions, bacteria, and gut microflora. Some of these pathogens are statistically associated with human obesity, but their causative role has not been established. If relevant to humans, “Infectobesity” would be a relatively novel, yet extremely significant medical concept. A new perspective about the infectious aetiology of obesity would stimulate research to assess the contribution of infectious agents to obesity and possibly to prevent or treat obesity of infectious origin. A recently published review article sets out to do just that (Infectobesity: obesity of infectious origin. Adv Food Nutr Res. 2007 52: 61-102)
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The first obesity-promoting pathogen to be reported was canine distemper virus, a paramyxovirus which infects dogs (A virally induced obesity syndrome in mice. 1982 Science 216: 885). Although this was an interesting observation, since canine distemper virus does not infect humans, comparatively little was made of this finding. But how could a virus infection cause animals to become obese? In 1982 Michael Oldstone and colleagues reported a novel way by which viruses may cause disease, the “hit-and-run” model (Virus-induced alterations in homeostasis: alteration in differentiated functions of infected cells in vivo. 1982 Science 218: 1125-1127). The virus replicates in cells which make growth hormone, disrupting homeostasis and decreasing growth hormone synthesis but without producing any cell death or inflammation. The effect of CDV on the hypothalamus may initiate changes that would continue to promote obesity in animals even months after the acute infection, suggesting a “hit-and-run” effect may have occurred (Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus. J Virol. 1999 73:7317-7327).
In 1983, Rous-associated virus-7 (RAV-7) was the second pathogen reported to cause obesity. RAV-7 is an avian retrovirus http://www.microbiologybytes.com/virology/Retroviruses.html found in domesticated poultry (Rous-associated virus type 7 induces a syndrome in chickens characterized by stunting and obesity. Infect Immun. 1983 39: 410-422). In this case, a decrease in thyroid hormone levels is the major metabolic change that may explain the obesity observed. Chlamydia pneumoniae is the first bacterium reported to be associated with increased body mass index (BMI) in humans. A number of epidemiological studies have linked infection with this organism to increased weight, although other studies have failed to find any connection. Unlike the organisms previously mentioned, experimental inoculation of animals with this organism to study the effect on body weight has not been reported, and so the link remains somewhat uncertain. Scrapie is a neurodegenerative prion disease of sheep and goats. Much of the work with scrapie has been performed using mice as a model, and scrapie has been reported to cause obesity in mice. Unlike other biological properties of scrapie, this effect is not dependent on the strain involved, although it is dependent on the route of inoculation. Scrapie-induced obesity is related to changes in the central nervous system (CNS) and neuroendocrine dysfunction in infected mice. Although a number of human prion diseases are known, the relevance of these findings in rodents to obesity in humans has not been established. Borna disease virus (BDV) is an enveloped, nonsegmented, negative-stranded RNA virus belonging to the Mononegavirales. Infection with BDV causes psychological as well as physical symptoms. BDV can cause obesity in experimentally infected rats, although only certain strains of the virus seem to do this. In this case, weight gain may be due to inflammatory lesions due to virus antigen expression in brain, especially in the hypothalamus, which is known to regulate body weight and food intake.
Finally, four strains of adenovirus have been reported to be adipogenic pathogens. Avian adenovirus SMAM-1 causes fat deposition (adiposity) in chickens, but also shows a serological association with human obesity (Association of adenovirus infection with human obesity. Obes Res. 1997 5: 464-9). This was the first virus to be linked with human obesity. It has been suggested that SMAM-1 infection could impair normal liver function, causing fatty liver and decreasing cholesterol and triglyceride levels in the blood. Subsequently, adenovirus types 5, 36 and 37 have also been shown cause obesity in animals. Of these, Ad-36 is the best studied. Sero-epidemiological studies show association between Ad-36 antibodies and human obesity, although the exact mechanism of
adipogenic action in vivo remains unknown. Of the 50 known serotypes of human adenovirus, only these three seem to cause obesity.
The jury is out on the significance of these findings to public health, but with increasing emphasis on obesity, they cannot safely be ignored. In the meantime, unless you’re listening to this podcast in the gym, get off your butt and take some exercise!
Acknowledgment: My thanks to Dr Nikhil Dhurandhar for his assistance with this article.
There have been three cases of mad cow disease in the USA. The first, in December 2003 in Washington state, was in a cow that had been imported from Canada. The second, in 2005, was in a Texas-born cow. The third was confirmed last year in an Alabama cow. The U.S. Agriculture Department currently tests less than one percent of slaughtered cows for the disease, which can be fatal to humans who eat tainted beef. But Kansas-based meat packing firm Creekstone Farms Premium Beef wants to test all of its cows. Larger meat companies feared that move because, if Creekstone tested its meat and advertised it as safe, they might have to perform the expensive test, too. A U.S. federal judge ruled in March that such tests must be allowed. The ruling was to take effect from June 1, but the Agriculture Department says it will appeal, delaying testing until the court challenge is settled.
In France, despite the ban of meat-and-bone meal (MBM) in cattle feed, bovine spongiform encephalopathy (BSE) was detected in hundreds of cattle born after the ban. To study the role of MBM, animal fat, and dicalcium phosphate on the risk for BSE after the feed ban, we conducted a spatial analysis of the feed industry. We used data from 629 BSE cases as well as on use of each byproduct and market area of the feed factories. Only use of MBM was spatially linked to risk for BSE, which highlights cross-contamination in feed factories as the most probable source of infection after the feed ban. In France, meat-and-bone meal (MBM) has been banned from cattle feed since July 30, 1990. However, through January 1, 2007, 957 cases of bovine spongiform encephalopathy (BSE) have been detected in cattle born after the ban. These cases provide evidence that BSE control has not been entirely effective, which poses a concern because BSE is a zoonotic disease, a source of variant Creutzfeldt-Jakob disease (vCJD). Until now, 158 definite or probable cases of vCJD in humans have been detected in the United Kingdom (www.cjd.ed.ac.uk/figures.htm) and 21 in France (www.invs.sante.fr/recherche). Achieving 100% control of the spread of BSE is a major challenge, important for human health but limited by economic constraints.
Researchers from NYU School of Medicine in New York say they have developed a vaccine which stops mice developing prion disease after experimental infection. Mice were orally vaccinated with an attenuated Salmonella strain which expressed the prion protein. Some (but not all) of the animals responded well to the vaccine and developed high levels of antibodies in their blood. These mice showed no symptoms of prion disease 400 days after infection (it normally takes 120 days for mice to develop the disease after deliberate inoculation). The mice with low levels of antibodies also had a significant delay in the onset of the disease, although symptoms did eventually appear in these animals. Much more work will be needed before the vaccine could be considered for use in humans.
PLoS Pathogens is two years old, and to celebrate, they’ve just published a list of the top ten papers downloaded from September 2005 to July 2007, so if you need to catch up on your reading:
In France, despite the ban of meat-and-bone meal (MBM) in cattle feed, bovine spongiform encephalopathy (BSE) was detected in hundreds of cattle born after the ban. To study the role of MBM, animal fat, and dicalcium phosphate on the risk for BSE after the feed ban, we conducted a spatial analysis of the feed industry. We used data from 629 BSE cases as well as on use of each byproduct and market area of the feed factories. Only use of MBM was spatially linked to risk for BSE, which highlights cross-contamination in feed factories as the most probable source of infection after the feed ban. In France, meat-and-bone meal (MBM) has been banned from cattle feed since July 30, 1990. However, through January 1, 2007, 957 cases of bovine spongiform encephalopathy (BSE) have been detected in cattle born after the ban. These cases provide evidence that BSE control has not been entirely effective, which poses a concern because BSE is a zoonotic disease, a source of variant Creutzfeldt-Jakob disease (vCJD). Until now, 158 definite or probable cases of vCJD in humans have been detected in the United Kingdom (
Researchers from NYU School of Medicine in New York say they have developed a vaccine which stops mice developing 