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Vidya P. Nair Saumya Anang Chandru Subramani Abhilasha Madhvi Karishma Bakshi Akriti Srivastava Shalimar Baibaswata Nayak Ranjith Kumar CT Milan Surjit 《PLoS pathogens》2016,12(4)
Hepatitis E virus (HEV) causes acute hepatitis in many parts of the world including Asia, Africa and Latin America. Though self-limiting in normal individuals, it results in ~30% mortality in infected pregnant women. It has also been reported to cause acute and chronic hepatitis in organ transplant patients. Of the seven viral genotypes, genotype-1 virus infects humans and is a major public health concern in South Asian countries. Sporadic cases of genotype-3 and 4 infection in human and animals such as pigs, deer, mongeese have been reported primarily from industrialized countries. Genotype-5, 6 and 7 viruses are known to infect animals such as wild boar and camel, respectively. Genotype-3 and 4 viruses have been successfully propagated in the laboratory in mammalian cell culture. However, genotype-1 virus replicates poorly in mammalian cell culture and no other efficient model exists to study its life cycle. Here, we report that endoplasmic reticulum (ER) stress promotes genotype-1 HEV replication by inducing cap-independent, internal initiation mediated translation of a novel viral protein (named ORF4). Importantly, ORF4 expression and stimulatory effect of ER stress inducers on viral replication is specific to genotype-1. ORF4 protein sequence is mostly conserved among genotype-1 HEV isolates and ORF4 specific antibodies were detected in genotype-1 HEV patient serum. ORF4 interacted with multiple viral and host proteins and assembled a protein complex consisting of viral helicase, RNA dependent RNA polymerase (RdRp), X, host eEF1α1 (eukaryotic elongation factor 1 isoform-1) and tubulinβ. In association with eEF1α1, ORF4 stimulated viral RdRp activity. Furthermore, human hepatoma cells that stably express ORF4 or engineered proteasome resistant ORF4 mutant genome permitted enhanced viral replication. These findings reveal a positive role of ER stress in promoting genotype-1 HEV replication and pave the way towards development of an efficient model of the virus. 相似文献
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Noviandi CT Razzazi E Agus A Böhm J Hulan HW Wedhastri S Maryudhani YB Nuryono Sardjono Leibetseder J 《Mycotoxin Research》2001,17(2):174-177
A survey was conducted between 1998–1999 to evaluate the level of aflatoxin B1 (AfB1) contamination in some selected Indonesian food products, mainly peanuts and peanut products for sale in supermarkets or traditional markets in Yogyakarta, Indonesia. Quantitative analysis was carried out on 118 samples using the ELISA (Enzyme-Linked Immunosorbent Assay) technique. The results indicate that (61.1%) samples were contaminated with AfB1 at range 2.0 to 249.0 μg/kg. Approximately 50% of the baby food products analysed were contaminated with AfB1 and the maximum level found was 7.0 μg/kg. In corn products and fermented products, AfB1 was detected in 66.7 and 50.0% of samples, respectively. A level as high as 5.6 μg/kg of AfB1 was found in the corn and 6.0 μg/kg in fermented product. AfB1 was also detected in all rice products, feed products, and other processed products at levels of up to 7.0, 27.0, and 26.0 μg/kg, respectively. 相似文献