Viral Structural Proteins

病毒结构蛋白质类
  • 文章类型: Journal Article
    我们观察到不同人群的SARS-CoV-2蛋白的预测主要组织相容性复合物II(MHCII)表位呈递存在实质性差异,但预测的MHCI表位呈递仅存在微小差异。这种预测的表位MHC覆盖率的比较显示,感染传播的早期阶段(直到达到128例观察到的感染病例后的第15天)与病死率呈高度显着负相关。具体来说,这是在不同群体中观察到的MHCII类呈递的病毒刺突蛋白(p值:0.0733线性回归),包膜蛋白(p值:0.023),和膜蛋白(p值:0.00053),这表明在一些国家观察到的COVID-19的高病死率似乎与MHCII类呈递不良有关,因此对这些病毒包膜蛋白的适应性免疫反应较弱。我们的结果强调了SARS-CoV-2结构蛋白在早期感染传播中的免疫控制中的普遍重要性,这是各国进行的全球人口普查并考虑了病死率的结果。其他因素如卫生系统和控制措施在早期传播后变得更加重要。我们的研究应鼓励进一步研究MHCII等位基因作为COVID-19的潜在危险因素,包括评估当地人群和特定等位基因分布。
    We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.
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  • 文章类型: Case Reports
    A fatal case of enterovirus 71 infection with pulmonary edema and rhombencephalitis occurred in Brest, France, in April 2007. The virus was identified as subgenogroup C2. This highly neurotropic enterovirus merits specific surveillance outside the Asia-Pacific region.
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  • 文章类型: Journal Article
    背景:2008年,甲型肝炎的流行病学转变导致了韩国持续的全社区爆发。
    目的:评估与甲型肝炎病毒(HAV)传播相关的危险因素,并分析持续全社区爆发的循环基因型。
    方法:以医院为基础的病例对照研究于4月至8月在首尔一所拥有850张床位的大学医院进行,2008.对于HAV分离株的分子分析,扩增并测序了VP1区的488bp基因片段。
    结果:在多变量逻辑回归模型中,按年龄调整的HAV感染的危险因素为与甲型肝炎病例接触(OR3.98,95%CI:1.36-11.66),儿童年龄<或=5岁(OR3.43,95%CI:1.32-8.87),食用未煮熟的生菜(OR3.98,95%CI:1.83-8.68)或胡萝卜(OR2.38,95%CI:2.38-5.09),饮用由净水器提供的自来水(OR3.68,95%CI:1.62-8.37)或便携式泉水(OR2.71,95%CI:1.11-6.62),外出就餐(OR3.87,95%CI:1.53-9.78)。分析的所有分离株都属于基因型IIIA。在分离物之间测序的VP1区域中存在42个核苷酸差异。氨基酸序列彼此相同。
    结论:我们的研究表明,零星污染的食物或水源以及人与人之间的传播可能导致持续的全社区HAV爆发,并且先前存在的显性基因型IA可能被基因型IIIA取代,成为韩国的主要流行菌株。我们的调查结果敦促卫生当局为HAV疫苗接种和疫情控制制定公开指南。
    BACKGROUND: The epidemiological shift of hepatitis A has contributed to a sustained community-wide outbreak in Korea during 2008.
    OBJECTIVE: To assess the risk factors associated with hepatitis A virus (HAV) propagation, and to analyze the circulating genotype in the sustained community-wide outbreak.
    METHODS: The hospital-based case-control study was conducted in an 850-bed university hospital in Seoul from April to August, 2008. For molecular analysis of HAV isolates, a 488-bp gene fragment of the VP1 region was amplified and sequenced.
    RESULTS: In the multivariated logistic regression model, the risk factors of HAV infection adjusted by age were contacts with hepatitis A case (OR 3.98, 95% CI: 1.36-11.66), residence with child aged CONCLUSIONS: Our study suggests that sporadically contaminated food- or water-borne sources as well as person-to-person transmission might lead a sustained community-wide HAV outbreak and pre-existing dominant genotype IA might be replaced with genotype IIIA as a major epidemic strain in Korea. Our findings urge the health authority to make public guidelines for HAV vaccination and outbreak control.
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  • 文章类型: Journal Article
    BACKGROUND: Human bocavirus (HBoV) was recently discovered in children with respiratory tract disease and gastroenteritis. The causative role of HBoV in human gastroenteritis remains uncertain, and, to our knowledge, no previous case-control study has studied the relationship between HBoV and gastroenteritis.
    METHODS: We conducted a case-control study that examined stool samples from 397 children with diarrhea and from 115 asymptomatic control subjects. HBoV was detected using polymerase chain reaction. Real-time polymerase chain reaction was used to quantify the HBoV loads in case and control groups. Common enteric viruses were examined using enzyme-linked immunosorbent assays, polymerase chain reaction, and reverse-transcription polymerase chain reaction.
    RESULTS: At least 1 viral agent was discovered in 60.2% of cases. HBoV was detected in 14 samples, and 9 were coinfected with either rotavirus (7 of 14 samples) or human calicivirus (2 of 14). Many (8 [57.1%] of 14) of the HBoV infections occurred during September-December 2006. Most (12 [85.7%]) of the HBoV-infected children were 7-18 months of age. The percentage of children with HBoV infection did not differ significantly between case patients and control subjects (3.5% vs. 3.5%), and the statistical analysis did not support a correlation between HBoV infection and more-severe clinical symptoms. The viral load differences between the 2 groups were not statistically significant (P = .09, by log-normal Student\'s t test). In addition, the VP1/VP2 partial gene of HBoV from case patients and control subjects showed minimal sequence variation.
    CONCLUSIONS: A single genetic lineage of HBoV was revealed in persons in China. Despite its high prevalence in stool samples, our study does not support a causative role of HBoV in gastroenteritis.
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  • 文章类型: Journal Article
    猫杯状病毒的亚基因组mRNA是双顺反子,两个顺反子由四个核苷酸重叠,..AUGA.上游顺反子编码75kDa的主要衣壳蛋白前体(前VP1),下游顺反子是10kDa的次要衣壳蛋白。网织红细胞裂解物中的翻译动力学表明,下游顺反子通过终止-重新引发过程翻译,这在不需要eIF4G或eIF4F复合体方面是不寻常的。重新开始需要前VP1ORF的3'末端87个核苷酸(nt),但没有其他病毒序列。由于其与该87-nt元件的邻近性而选择重新起始位点,而不是它靠近前VP1ORF终止密码子,虽然这必须位于不超过约30nt下游的重新开始密码子。该87-nt元件显示结合40S核糖体亚基和起始因子eIF3,并且添加补充eIF3提高了重新起始效率。在重新起始中有缺陷的突变体显示对eIF3或有缺陷的40S亚基结合(或两者)的亲和力降低。这些结果表明了一种机制,其中在终止后核糖体的拆解过程中形成的一些eIF3/40S复合物在获得eIF2/GTP/Met-tRNA三元复合物后适合于重新启动的位置与该87-nt元件结合。
    The subgenomic mRNA of feline caliciviruses is bicistronic with the two cistrons overlapping by four nucleotides, ..AUGA. The upstream cistron encodes a 75-kDa major capsid protein precursor (pre-VP1), and the downstream cistron a 10-kDa minor capsid protein. The kinetics of translation in reticulocyte lysates show that the downstream cistron is translated by a termination-reinitiation process, which is unusual in not requiring eIF4G or the eIF4F complex. Reinitiation requires the 3\'-terminal 87 nucleotides (nt) of the pre-VP1 ORF, but no other viral sequences. The reinitiation site is selected by virtue of its proximity to this 87-nt element, and not its proximity to the pre-VP1 ORF stop codon, although this must be located not more than approximately 30 nt downstream from the restart codon. This 87-nt element was shown to bind 40S ribosomal subunits and initiation factor eIF3, and addition of supplementary eIF3 enhanced reinitiation efficiency. Mutants defective in reinitiation showed reduced affinity for eIF3 or defective 40S subunit binding (or both). These results suggest a mechanism in which some of the eIF3/40S complexes formed during disassembly of post-termination ribosomes bind to this 87-nt element in a position appropriate for reinitiation following acquisition of an eIF2/GTP/Met-tRNA i ternary complex.
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  • 文章类型: Journal Article
    PSA is a temperate phage isolated from Listeria monocytogenes strain Scott A. We report its complete nucleotide sequence, which consists of a linear 37 618 bp DNA featuring invariable, 3\'-protruding single stranded (cohesive) ends of 10 nucleotides. The physical characteristics were confirmed by partial denaturation mapping and electron microscopy of DNA molecules. Fifty-seven open reading frames were identified on the PSA genome, which are apparently organized into three major transcriptional units, in a life cycle-specific order. Functional assignments could be made to 33 gene products, including structural proteins, lysis components, DNA packaging proteins, lysogeny control functions and replication proteins. Bioinformatics demonstrated relatedness of PSA to phages infecting lactic acid bacteria and other low G + C Gram-positives, but revealed only few similarities to Listeria phage A118. Virion proteins were analysed by amino acid sequencing and mass spectrometry, which enabled identification of major capsid and tail proteins, a tape measure and a putative portal. These analyses also revealed an unusual form of translational frameshifting, which occurs during decoding of the mRNAs specifying the two major structural proteins. Frameshifting yields different length forms of Cps (gp5) and Tsh (gp10), featuring identical N-termini but different C-termini. Matrix-assisted laser-desorption ionization mass spectrometry (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS) of tryptic peptide fragments was used to identify the modified C-termini of the longer protein species, by demonstration of specific sequences resulting from + 1 programmed translational frameshifting. A slippery sequence with overlapping proline codons near the 3\' ends of both genes apparently redirects the ribosomes and initiates the recoding event. Two different cis-acting factors, a shifty stop and a pseudoknot, presumably stimulate frameshifting efficiency. PSA represents the first case of + 1 frameshifting among dsDNA phages, and appears to be the first example of a virus utilizing a 3\' pseudoknot to stimulate such an event.
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  • 文章类型: Journal Article
    We report the cloning and sequencing of the putative structural region of the hepatitis C virus (HCV) genome (2229 nucleotides) from an isolate derived from a British case of chronic sporadic non-A, non-B hepatitis. The overall sequence shows a higher similarity with one type of HCV, HCV1 (92%), than with HCV2 (80%), is very highly conserved at the 5\' end (99%) preceding the long open reading frame, is well conserved also in the putative core region (90 to 97%), but shows marked variation in the putative envelope region, particularly in the envelope 2/non-structural 1 region (70%). The putative core gene was cloned in pJ3 omega under the early simian virus 40 promoter and expressed in human hepatoma cells. A predominantly cytoplasmic 22K polypeptide was expressed which was antigenically reactive with serum from chronically infected HCV patients.
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