69 research outputs found
A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus
The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses
Dermatitis caused by the tropical fowl mite Ornithonyssus bursa (Berlese) (Acari: Macronyssidae): a case report in humans
Abstract: We herein report human dermatitis caused by the tropical fowl mite Ornithonyssus bursa (Berlese). The cases occurred in an apartment in a residential district of Porto Alegre City, State of Rio Grande do Sul, Brazil, where three members of the same family presented with pruritic lesions on the arms and legs. On inspecting the bathroom, several mites measuring approximately 1.0mm in length were observed coming from a nest of Rufous Hornero, Furnarius rufus (Gmelin). This is the first report of O. bursa in the urban area of Porto Alegre City, from a nest of F. rufus that bites humans
Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia
BACKGROUND: Yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. The disease is usually transmitted among wild rodents through a flea vector. The sources and routes of transmission of plague are poorly researched in Africa, yet remains a concern in several sub-Saharan countries. In Zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenance and propagation of the bacterium. In this study, we undertook plague surveillance by using PCR amplification of the plasminogen activator gene in fleas. FINDINGS: Xenopsylla species of fleas were collected from 83 rodents trapped in a plague endemic area of Zambia. Of these rodents 5 had fleas positive (6.02%) for Y. pestis plasminogen activator gene. All the Y. pestis positive rodents were gerbils. CONCLUSIONS: We conclude that fleas may be responsible in the transmission of Y. pestis and that PCR may provide means of plague surveillance in the endemic areas of Zambia
Reproductive Phase Locking of Mosquito Populations in Response to Rainfall Frequency
The frequency of moderate to heavy rainfall events is projected to change in response to global warming. Here we show that these hydrologic changes may have a profound effect on mosquito population dynamics and rates of mosquito-borne disease transmission. We develop a simple model, which treats the mosquito reproductive cycle as a phase oscillator that responds to rainfall frequency forcing. This model reproduces observed mosquito population dynamics and indicates that mosquito-borne disease transmission can be sensitive to rainfall frequency. These findings indicate that changes to the hydrologic cycle, in particular the frequency of moderate to heavy rainfall events, could have a profound effect on the transmission rates of some mosquito-borne diseases
Mechanistic model for predicting the seasonal abundance of Culicoides biting midges and the impacts of insecticide control
Seroprevalence report on tick-borne encephalitis virus and Crimean-Congo hemorrhagic fever virus among Malaysian’s farm workers
Reassessment of pre-industrial fire emissions strongly affects anthropogenic aerosol forcing
Uncertainty in pre-industrial natural aerosol emissions is a major component of the overall uncertainty in the radiative forcing of climate. Improved characterisation of natural emissions and their radiative effects can therefore increase the accuracy of global climate model projections. Here we show that revised assumptions about pre-industrial fire activity result in significantly increased aerosol concentrations in the pre-industrial atmosphere. Revised global model simulations predict a 35% reduction in the calculated global mean cloud albedo forcing over the Industrial Era (1750–2000 CE) compared to estimates using emissions data from the Sixth Coupled Model Intercomparison Project. An estimated upper limit to pre-industrial fire emissions results in a much greater (91%) reduction in forcing. When compared to 26 other uncertain parameters or inputs in our model, pre-industrial fire emissions are by far the single largest source of uncertainty in pre-industrial aerosol concentrations, and hence in our understanding of the magnitude of the historical radiative forcing due to anthropogenic aerosol emissions
- …