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Single Mutation in the Flavivirus Envelope Protein Hinge Region Increases Neurovirulence for Mice and Monkeys but Decreases Viscerotropism for Monkeys: Relevance to Development and Safety Testing of Live, Attenuated Vaccines
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Thomas P. Monath Juan Arroyo Inessa Levenbook Zhen-Xi Zhang John Catalan Ken Draper Farshad Guirakhoo 《Journal of virology》2002,76(4):1932-1943
A chimeric yellow fever (YF) virus/Japanese encephalitis (JE) virus vaccine (ChimeriVax-JE) was constructed by insertion of the prM-E genes from the attenuated JE virus SA14-14-2 vaccine strain into a full-length cDNA clone of YF 17D virus. Passage in fetal rhesus lung (FRhL) cells led to the emergence of a small-plaque virus containing a single Met-->Lys amino acid mutation at E279, reverting this residue from the SA14-14-2 to the wild-type amino acid. A similar virus was also constructed by site-directed mutagenesis (J. Arroyo, F. Guirakhoo, S. Fenner, Z.-X. Zhang, T. P. Monath, and T. J. Chambers, J. Virol. 75:934-942, 2001). The E279 mutation is located in a beta-sheet in the hinge region of the E protein that is responsible for a pH-dependent conformational change during virus penetration from the endosome into the cytoplasm of the infected cell. In independent transfection-passage studies with FRhL or Vero cells, mutations appeared most frequently in hinge 4 (bounded by amino acids E266 to E284), reflecting genomic instability in this functionally important region. The E279 reversion caused a significant increase in neurovirulence as determined by the 50% lethal dose and survival distribution in suckling mice and by histopathology in rhesus monkeys. Based on sensitivity and comparability of results with those for monkeys, the suckling mouse is an appropriate host for safety testing of flavivirus vaccine candidates for neurotropism. After intracerebral inoculation, the E279 Lys virus was restricted with respect to extraneural replication in monkeys, as viremia and antibody levels (markers of viscerotropism) were significantly reduced compared to those for the E279 Met virus. These results are consistent with the observation that empirically derived vaccines developed by mouse brain passage of dengue and YF viruses have increased neurovirulence for mice but reduced viscerotropism for humans. 相似文献
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Farshad M Barbezat M Flüeler P Schmidlin F Graber P Niederer P 《Journal of biomechanics》1999,32(4):417-425
The objective of this study was an investigation of the material properties of the fresh pig kidney and parametric characterization of its elastic and inelastic material behavior. The material investigation included density measurements, uniaxial as well as three-dimensional compression tests, tensile tests. and shear tests on the samples extracted from the fresh pig kidney. For comparison, density measurements on a number of soft synthetic materials were also performed. Compression tests on the radial and the tangential specimens from the cortex tissue were performed at various loading rates. Three-axial compression tests were performed on the cortex tissues placed in a compression chamber. Shear tests were performed by punching a cylinder into a slice of the cortex. Tensile tests were carried out on the outer capsule. For characterization of the material behavior, a non-linear theoretical simulation based on a two parameter Blatz model was used. For characterization of the time-dependent behavior of the pig kidney cortex, a four-parameter linear viscoelastic model was employed. From the present experimental and theoretical studies, a number of conclusions were derived: (1) The general behavior of the pig kidney cortex samples under compression showed the general non-linear features typical of the soft tissues; the stress strain diagram was composed of a very flat part at very low stress level to about 30% relative deformation which was followed by a steeply rising stiffening leading to the radial rupture of samples marked by a maximum nominal rupture strain of about 50%. (2) The uniaxial compression tests on the radial and the tangential samples from the cortex tissue showed an increase of the rupture stress with the increase in the loading rate, but a decrease in the related rupture strain. (3) The long-term uniaxial compression tests on the cortex specimens under sustained constant load showed an instantaneous deformation followed by a creep response which eventually approached an asymptote. (4) Simulation of the non-linear material behavior of the cortex tissue under uniaxial compression by the Blatz model gave two pairs of material parameters for the cortex in the radial and the tangential directions. Furthermore, fitting of the assumed four-parameter linear viscoelastic model with the experimental data resulted in the viscoelastic material parameters. 相似文献
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Kamyar Khoshnevisan Maryam Chehrehgosha Melissa Conant Amir Mohammad Meftah Hadi Baharifar Hanieh-Sadat Ejtahed Pooneh Angoorani Morteza Gholami Farshad Sharifi Hassan Maleki Bagher Larijani Mohammad Reza Khorramizadeh 《Journal of applied microbiology》2022,132(6):4186-4207
Tryptophan (Trp), an α-amino acid, is the precursor of serotonin (5-hydroxytryptamine, 5-HT), which is involved in a variety of features of metabolic function and human nutrition. Evidence highlights the role of Trp metabolites (exclusively 5-HT) in the gastrointestinal (GI) tract; however, the mechanisms of action involved in the release of 5-HT in the GI tract are still unknown. Considering the fact that variations of 5-HT may facilitate the growth of certain GI disorders, gaining a better understanding of the function and release of 5-HT in the GI tract would be beneficial. Additionally, investigating Trp metabolism may clarify the relationship between Trp and gut microbiota. It is believed that other metabolites of Trp (mostly that of the kynurenine pathway) may play a significant role in controlling gut microbiota function. In this review, we have attempted to summarize the current research investigating the relationship of gut microbiota, Trp and 5-HT metabolism (with particular attention paid to their metabolite type, as well as a discussion of the research methods used in each study). Taking together, regarding the role that Trp/5-HT plays in a range of physical and mental diseases, the gut bacterial types, as well as the related disorders, have been exclusively considered. 相似文献
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Majid Eslami Morvarid Shafiei Abdolmajid Ghasemian Saeid Valizadeh Ali Hussein Al-Marzoqi Seyyed Khalil Shokouhi Mostafavi Farshad Nojoomi Seyede Amene Mirforughi 《Journal of cellular physiology》2019,234(8):12415-12421
Mycobacterium avium complex (MAC) and Mycobacterium avium paratuberculosis (MAP) cause zoonotic infections transmitted by birds and livestock herds. These pathogens have remained as serious economic and health threats in most areas of the world. As zoonotic diseases, the risk of development of occupational disease and even death outcome necessitate implementation of control strategies to prevent its spread. Zoonotic MAP infections include Crohn’s disease, inflammatory bowel disease, ulcerative colitis, sarcoidosis, diabetes mellitus, and immune-related diseases (such as Hashimoto’s thyroiditis). Paratuberculosis has classified as type B epidemic zoonotic disease according to world health organization which is transmitted to human through consumption of dairy and meat products. In addition, MAC causes pulmonary manifestations and lymphadenitis in normal hosts and human immunodeficiency virus (HIV) progression (by serotypes 1, 4, and 8). Furthermore, other subspecies have caused respiratory abscesses, neck lymph nodes, and disseminated osteomyelitis in children and ulcers. However, the data over the occupational relatedness of these subspecies is rare. These agents can cause occupational infections in susceptible herd breeders. Several molecular methods have been recognized as proper strategies for tracking the infection. In this study, some zoonotic aspects, worldwide prevalence and control strategies regarding infections due to MAP and MAC and related subspecies has been reviewed. 相似文献
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Hemmati Farshad Hemmati-Dinarvand Mohsen Karimzade Marziye Rutkowska Daria Eskandari Mohammad Hadi Khanizadeh Sayyad Afsharifar Alireza 《Biotechnology letters》2022,44(1):45-57
Biotechnology Letters - After its emergence in late 2019 SARS-CoV-2 was declared a pandemic by the World Health Organization on 11 March 2020 and has claimed more than 2.8 million lives. There has... 相似文献
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Moradzad Mohammad Abdi Mohammad Sheikh Esmaeili Farshad Ghaderi Dana Rahmani Khaled Moloudi Mohammad Raman Vahabzadeh Zakaria 《Molecular biology reports》2022,49(7):5927-5937
Molecular Biology Reports - Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder with complicated pathophysiology. Trimethylamine-N-oxide (TMAO) has been thought to be correlated... 相似文献
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Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease
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Silvia Maioli Maria Lodeiro Paula Merino‐Serrais Farshad Falahati Wasim Khan Elena Puerta Alina Codita Roberto Rimondini Maria J. Ramirez Andrew Simmons Francisco Gil‐Bea Eric Westman Angel Cedazo‐Minguez the Alzheimer's Disease Neuroimaging Initiative 《Aging cell》2015,14(1):122-129
Several studies support the relation between leptin and Alzheimer's disease (AD). We show that leptin levels in CSF are unchanged as subjects progress to AD. However, in AD hippocampus, leptin signalling was decreased and leptin localization was shifted, being more abundant in reactive astrocytes and less in neurons. Similar translocation of leptin was found in brains from Tg2576 and apoE4 mice. Moreover, an enhancement of leptin receptors was found in hippocampus of young Tg2576 mice and in primary astrocytes and neurons treated with Aβ1‐42. In contrast, old Tg2576 mice showed decreased leptin receptors levels. Similar findings to those seen in Tg2576 mice were found in apoE4, but not in apoE3 mice. These results suggest that leptin levels are intact, but leptin signalling is impaired in AD. Thus, Aβ accumulation and apoE4 genotype result in a transient enhancement of leptin signalling that might lead to a leptin resistance state over time. 相似文献
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A proteome-wide protein interaction map for Campylobacter jejuni 总被引:2,自引:0,他引:2
Parrish JR Yu J Liu G Hines JA Chan JE Mangiola BA Zhang H Pacifico S Fotouhi F DiRita VJ Ideker T Andrews P Finley RL 《Genome biology》2007,8(7):R130-19