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2. chinaXiv:201705.00713 [pdf]

Spike Protein, S, of Human Coronavirus HKU1: Role in Viral Life Cycle and Application in Antibody Detection

Chan, Che-Man; Woo, Patrick C. Y; Lau, Susanna K. P; Tse, Herman; Chen, Hong-Lin; Li, Feng; Zheng, Bo-Jian; Chen, Ling; Huang, Jian-Dong; Yuen, Kwok-Yung
Subjects: Biology >> Biomedical Laboratory Science

We recently described the discovery, genome, clinical features, genotypes and evolution of a novel and global human respiratory virus named human coronavirus HKU1 (HCoV-HKU1) which is not yet culturable. We expressed a C-terminal FLAG-tagged CoV-HKU1 spike (S) protein by the Semliki Forest Virus (SFV) system and investigated its maturation profile. Pulse chase labeling revealed that S-FLAG was expressed as high-mannose N-glycans of monomers and trimers. It was predominantly cleaved into subdomains S1 and S2 during maturation. S1 was secreted into the medium. Immunofluorescence analysis visualized S along the secretory pathway from endoplasmic reticulum to plasma membrane. Cleavage of S and release of HCoV-HKU1 S pseudotyped virus were inhibited by furin or furin-like enzyme inhibitors. The cell-based expressed full-length S-FLAG could be recognized by the convalescent serum obtained from a patient with HCoV-HKU1 pneumonia. The data suggest that the native form of HCoV-HKU1 spike expressed in our system can be used in developing serological diagnostic assay and in understanding the role of S in the viral life cycle. Exp Biol Med 233:1527-1536, 2008

submitted time 2017-05-10 Hits1952Downloads1054 Comment 0

3. chinaXiv:201605.01367 [pdf]

Commensal bacteria direct selective cargo sorting to promote symbiosis

Zhang, Qin; Pan, Ying; Yan, Ruiqing; Wang, Haifang; Zhang, Xinwen; Liu, Zhihua; Zeng, Benhua; Li, Wenxia; Wei, Hong; Liu, Zhihua
Subjects: Biology >> Biophysics >> Immunology

Mucosal immunity protects a host from intestinal inflammation and infection and is profoundly influenced by symbiotic bacteria. Here we report that in mice symbiotic bacteria directed selective cargo sorting in Paneth cells to promote symbiosis through Nod2, a cytosolic bacterial sensor, and the multifunctional protein kinase LRRK2, both encoded by inflammatory bowel disease (IBD)-associated genes. Commensals recruited Nod2 onto lysozyme-containing dense core vesicles (DCVs), which was required for DCV localization of LRRK2 and a small GTPase, Rab2a. Deficiency of Nod2, LRRK2 or Rab2a or depletion of commensals resulted in lysosomal degradation of lysozyme. Thus, commensal bacteria and host factors orchestrate the lysozyme-sorting process to protect the host from enteric infection, implicating Paneth cell dysfunction in IBD pathogenesis.

submitted time 2016-05-12 Hits2923Downloads1569 Comment 0

4. chinaXiv:201605.01355 [pdf]

KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum

Li, Ming Yuan; Kwok, Kevin; Siu, Yu Lam; Zhang, Jing Shu; Kudelko, Mateusz; Bruzzone, Roberto; Wang, Pei Gang; Li, Ming Yuan; Kwok, Kevin; Siu, Yu Lam; Zhang, Jing Shu; Kudelko, Mateusz; Bruzzone, Roberto; Wang, Pei Gang; Grandadam, Marc; Sayteng, Kouxiong; Lagache, Thibault; Olivo-Marin, Jean-Christophe; Lagache, Thibault; Olivo-Marin, Jean-Christophe
Subjects: Biology >> Biophysics >> Cell Biology

Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR by siRNA reduced egress of both DENV progeny and recombinant subviral particles (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM required three positively charged residues at the N terminus, whose mutation disrupted protein interaction and inhibited RSP transport from the ER to the Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR accumulation in the Golgi, phenocopied results obtained with mutagenized prME and KDELR knockdown. Our results have uncovered a function for KDELR as an internal receptor involved in DENV trafficking.

submitted time 2016-05-11 Hits1230Downloads676 Comment 0

5. chinaXiv:201605.01324 [pdf]

Molecular characteristics and evolutionary analysis of a very virulent infectious bursal disease virus

Li Zan; Zhu Ping; Qi XiaoLe; Ren XianGang; Wang XiaoMei; Cui Lei; Li Zan
Subjects: Biology >> Biophysics >> Biology

Infectious bursal disease virus (IBDV) poses a significant threat to the poultry industry. Viral protein 2 (VP2), the major structural protein of IBDV, has been subjected to frequent mutations that have imparted tremendous genetic diversity to the virus. To determine how amino acid mutations may affect the virulence of IBDV, we built a structural model of VP2 of a very virulent strain of IBDV identified in China, vvIBDV Gx, and performed a molecular dynamics simulation of the interaction between virulence sites. The study showed that the amino acid substitutions that distinguish vvIBDV from attenuated IBDV (H253Q and T284A) favor a hydrophobic and flexible conformation of beta-barrel loops in VP2, which could promote interactions between the virus and potential IBDV-specific receptors. Population sequence analysis revealed that the IBDV strains prevalent in East Asia show a significant signal of positive selection at virulence sites 253 and 284. In addition, a signal of co-evolution between sites 253 and 284 was identified. These results suggest that changes in the virulence of IBDV may result from both the interaction and the co-evolution of multiple amino acid substitutions at virulence sites.

submitted time 2016-05-11 Hits2510Downloads1374 Comment 0

6. chinaXiv:201605.01234 [pdf]

Ecdysone and Insulin Signaling Play Essential Roles in Readjusting the Altered Body Size Caused by the dGPAT4 Mutation in Drosophila

Yan, Yan; Wang, Hao; Chen, Hanqing; Lindstrom-Battle, Anya; Jiao, Renjie; Yan, Yan; Chen, Hanqing; Wang, Hao; Jiao, Renjie
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Body size is one of the features that distinguish one species from another in the biological world. Animals have developed mechanisms to control their body size during normal development. However, how animals cope with genetic alterations and/or environmental stresses to develop into normal-sized adults remain poorly understood. The ability of the animals to develop into a normal-sized adult after the challenges of genetic alterations and/or environmental stresses reveals a robustness of body size control. Here we show that the mutation of dGPAT4, a de novo synthase of lysophosphatidic acid, is a genetic alteration that triggers such a robust response of the animals to body size challenges in Drosophila. Loss of dGPAT4 leads to a severe delay of development, slow growth and resultant small-sized animals during the larval stages, but results in normal-sized adult flies. The robust body size adjustment of the dGPAT4 mutant is likely achieved by corresponding changes in ecdysone and insulin signaling, which is also manifested by compromised food intake. Thus, we propose that a strategy has been evolved by the animals to reach final body size when challenged by genetic alterations, which requires the coordinated ecdysone and insulin signaling.

submitted time 2016-05-11 Hits1389Downloads743 Comment 0

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