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排序方式: 共有139条查询结果,搜索用时 640 毫秒
101.
The quasispecies (extremely heterogeneous) nature of viral RNA genome populations: biological relevance--a review 总被引:32,自引:0,他引:32
Esteban Domingo Encarnación Martínez-Salas Francisco Sobrino Juan Carlos de la Torre Agustín Portela Juan Ortín Cecilio López-Galindez Pilar Pérez-Breña Nieves Villanueva Rafael Nájera Scott VandePol David Steinhauer Nicholas DePolo John Holland 《Gene》1985,40(1):1-8
We review evidence that cloned (or uncloned) populations of most RNA viruses do not consist of a single genome species of defined sequence, but rather of heterogeneous mixtures of related genomes (quasispecies). Due to very high mutation rates, genomes of a quasispecies virus population share a consensus sequence but differ from each other and from the consensus sequence by one, several, or many mutations. Viral genome analyses by sequencing, fingerprinting, cDNA cloning etc. indicate that most viral RNA populations (quasispecies) contain all possible single and double genomic site mutations and varying proportions of triple, quadruple, etc. site mutations. This quasispecies structure of RNA virus populations has many important theoretical and practical implications because mutations at only one or a few sites may alter the phenotype of an RNA virus. 相似文献
102.
Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1 总被引:1,自引:0,他引:1
Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication. We found that the EIF2S1-ATF4 pathway was activated and the AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work provides the first piece of evidence that expression of FMDV capsid protein VP2 can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV replication. In addition, we show that VP2 induced autophagy in a variety of mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin) polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and activation of the EIF2S1-ATF4 pathway. 相似文献
103.
Melissa S. Maginnis 《Journal of molecular biology》2018,430(17):2590-2611
Virus–receptor interactions play a key regulatory role in viral host range, tissue tropism, and viral pathogenesis. Viruses utilize elegant strategies to attach to one or multiple receptors, overcome the plasma membrane barrier, enter, and access the necessary host cell machinery. The viral attachment protein can be viewed as the “key” that unlocks host cells by interacting with the “lock”—the receptor—on the cell surface, and these lock-and-key interactions are critical for viruses to successfully invade host cells. Many common themes have emerged in virus–receptor utilization within and across virus families demonstrating that viruses often target particular classes of molecules in order to mediate these events. Common viral receptors include sialylated glycans, cell adhesion molecules such as immunoglobulin superfamily members and integrins, and phosphatidylserine receptors. The redundancy in receptor usage suggests that viruses target particular receptors or “common locks” to take advantage of their cellular function and also suggests evolutionary conservation. Due to the importance of initial virus interactions with host cells in viral pathogenesis and the redundancy in viral receptor usage, exploitation of these strategies would be an attractive target for new antiviral therapeutics. 相似文献
104.
Foot and mouth disease virus (FMDV) has been demonstrated to infect dendritic cells (DC) and reduced its ability to stimulate host immune responses. This study aimed to determine whether non-replicating FMDV could induce apoptosis of the host immune cells. In this study, we have demonstrated that bone morrow derived dendritic cells (BMDCs) were induced to undergo apoptosis in a dose-dependent manner, which was determined by the annexin-V staining, DNA fragmentation, and TUNEL staining methods, after they were treated with the chemically inactivated FMDV in vitro. The initiation of apoptosis was apparently via an interaction of the integrin receptor on BMDCs and the RGD motif within the VP1 capsid protein of FMDV. The initiation activated a cascade of apoptotic pathway including reduced expression of Bcl-2, activation of caspases, and release of cytochrome c from mitochondria. Pretreatment with BMDCs with LPS prevented the inactivated FMDV induced apoptosis, suggesting immature BMDCs are susceptible to such apoptosis. Taken together, the data demonstrate that the inactivated FMDV induces the apoptosis in BMDCs via the integrin receptor and subsequently triggers the apoptosis signal, suggesting that such induction of apoptosis is likely to impair immune responses against FMDV infection. 相似文献
105.
口蹄疫病毒NSP 3ABC基因在昆虫细胞中的分泌表达及其活性检测 总被引:3,自引:1,他引:2
用设计的特异引物,扩增得到了N-端带有6×His编码序列的口蹄疫病毒完整3ABC基因序列,并将其亚克隆入带有蜂毒溶血肽序列的穿梭质粒pMelBac-B中,构建了重组质粒pMel-3ABC。将该重组质粒与杆状病毒骨架DNABac-N-BlueTM共转染Sf9昆虫细胞,通过噬斑筛选和PCR鉴定,获得了含有目的基因的重组杆状病毒。重组病毒感染Sf9昆虫细胞,采用通过SDS-PAGE和Western blot检测,证明目的基因在昆虫细胞中得到了正确的表达,表达产物分泌至细胞培养上清中,并具有良好的生物活性。表达的目的蛋白经过镍柱亲和层析法纯化后,用间接ELISA方法检测与口蹄疫病毒感染动物血清的反应性,证明表达目的蛋白与感染动物血清有很好的反应性而与正常动物以及免疫动物血清不发生反应。该研究为建立一种更加敏感和特异的口蹄疫病毒感染动物与疫苗免疫动物的鉴别诊断方法奠定了基础。 相似文献
106.
用设计的特异引物,扩增得到了N-端带有6×His编码序列的口蹄疫病毒完整3ABC基因序列,并将其亚克隆入带有蜂毒溶血肽序列的穿梭质粒pMelBac-B中,构建了重组质粒pMel-3ABC。将该重组质粒与杆状病毒骨架DNA Bac-N-BlueTM共转染Sf9昆虫细胞,通过噬斑筛选和PCR鉴定,获得了含有目的基因的重组杆状病毒。重组病毒感染Sf9昆虫细胞,采用通过SDS-PAGE和Western blot检测,证明目的基因在昆虫细胞中得到了正确的表达,表达产物分泌至细胞培养上清中,并具有良好的生物活性。表达的目的蛋白经过镍柱亲和层析法纯化后,用间接ELISA方法检测与口蹄疫病毒感染动物血清的反应性,证明表达目的蛋白与感染动物血清有很好的反应性而与正常动物以及免疫动物血清不发生反应。该研究为建立一种更加敏感和特异的口蹄疫病毒感染动物与疫苗免疫动物的鉴别诊断方法奠定了基础。 相似文献
107.
Jaulent AM Fahy AS Knox SR Birtley JR Roqué-Rosell N Curry S Leatherbarrow RJ 《Analytical biochemistry》2007,368(2):130-137
Foot-and-mouth disease virus is a highly contagious pathogen that spreads rapidly among livestock and is capable of causing widespread agricultural and economic devastation. The virus genome is translated to produce a single polypeptide chain that subsequently is cleaved by viral proteases into mature protein products, with one protease, 3C(pro), carrying out the majority of the cleavages. The highly conserved nature of this protease across different viral strains and its crucial role in viral maturation and replication make it a very desirable target for inhibitor design. However, the lack of a convenient and high-throughput assay has been a hindrance in the characterization of potential inhibitors. In this article, we report the development of a continuous assay with potential for high throughput using fluorescence resonance energy transfer-based peptide substrates. Several peptide substrates containing the 3C-specific cleavage site were synthesized, varying both the positions and separation of the fluorescent donor and quencher groups. The best substrate, with a specificity constant k(cat)/K(M) of 57.6+/-2.0M(-1) s(-1), was used in inhibition assays to further characterize the protease's activity against a range of commercially available inhibitors. The inhibition profile of the enzyme showed characteristics of both cysteine and serine proteases, with the chymotrypsin inhibitor TPCK giving stoichiometric inhibition of the enzyme and allowing active site titration of the 3C(pro). 相似文献
108.
Shan-dian Gao Jun-zheng Du Hui-yun Chang Guo-zheng Cong Jun-jun Shao Tong Lin Shuai Song Qing-ge Xie 《中国病毒学》2010,25(1):18-26
In this study, the coding region of type O FMDV capsid protein VP1 and a series of codon optimized DNA sequences coding for
VP1 amino acid residues 141–160 (epitope1), tandem repeat 200–213 (epitope2 (+2)) and the combination of two epitopes (epitope1–2)
was genetically cloned into the prokaryotic expression vector pPROExHTb and pGEX4T-1, respectively. VP1 and the fused epitopes GST-E1, GST-E2 (+2) and GST-E1-2 were successfully solubly expressed
in the cytoplasm of Escherichia coli and Western blot analysis demonstrated they retained antigenicity. Indirect VP1-ELISA and epitope ELISAs were subsequently
developed to screen a panel of 80 field pig sera using LPB-ELISA as a standard test. For VP1-ELISA and all the epitope ELISAs,
there were clear distinctions between the FMDV-positive and the FMDV-negative samples. Cross-reactions with pig sera positive
to the viruses of swine vesicular disease virus that produce clinically indistinguishable syndromes in pigs or guinea pig
antisera to FMDV strains of type A, C and Asia1 did not occur. The relative sensitivity and specificity for the GST-E1 ELISA,
GST-E2 (+2), GST-E1-2 ELISA and VP1-ELISA in comparison with LPB-ELISA were 93.3% and 85.0%, 95.0% and 90%, 100% and 81.8%,
96.6% and 80.9% respectively. This study shows the potential use of the aforementioned epitopes as alternatives to the complex
antigens used in current detection for antibody to FMDV structural proteins. 相似文献
109.
Tao Jiang Zhong Liang Wei-wei Ren Juan Chen Xiao-ying Zhi Guang-yu Qi Xiang-tao Liu Xue-peng Cai 《中国病毒学》2011,26(1):30-39
A sandwich format immunochromatographic assay for detecting foot-and-mouth disease virus (FMDV) serotypes was developed. In
this rapid test, affinity purified polyclonal antibodies from Guinea pigs which were immunized with sucking-mouse adapted
FMD virus (A/AV88(L) strain) were conjugated to colloidal gold beads and used as the capture antibody, and affinity purified
polyclonal antibodies from rabbits which were immunized with cell-culture adapted FMD virus (A/CHA/09 strain) were used as
detector antibody. On the nitrocellulose membrane of the immunochromatographic strip, the capture antibody was laid on a sample
pad, the detector antibody was printed at the test line(T) and goat anti-guinea pigs IgG antibodies were immobilized to the
control line(C). The lower detection limit of the test for a FMDV 146S antigen is 11.7ng/ml as determined in serial tests
after the strip device was assembled and the assay condition optimization. No cross reactions were found with FMDV serotype
C, Swine vesicular disease (SVD), Vesicular stomatiti svirus (VSV) and vesicular exanthema of swine virus (VES) viral antigens
with this rapid test. Clinically, the diagnostic sensitivity of this test for FMDV serotypes A was 88.7% which is as same
as an indirect-sandwich ELISA. The specificity of this strip test was 98.2% and is comparable to the 98.7% obtained with indirect-sandwich
ELISA. This rapid strip test is simple, easy and fast for clinical testing on field sites; no special instruments and skills
are required, and the result can be obtained within 15 min. To our knowledge, this is the first rapid immunochromatogarpic
assay for serotype A of FMDV. 相似文献
110.