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1.
Varicella-zoster virus infects human dendritic cells (DCs). We found that VZV infection of DCs resulted in down-regulation of Fas expression on the surface of cells. VZV ORF47 was critical for replication of virus in human immature, but not mature DCs. Immature DCs infected with a mutant virus unable to express ORF47 expressed similar levels of a VZV immediate-early protein as cells infected with parental virus; however, cells infected with the ORF47 mutant expressed lower levels of glycoprotein E. Thus, in the absence of ORF47 protein, there is a block in viral replication between immediate-early and late gene expression. VZV unable to express ORF47 was severely impaired for spread of virus from DCs to melanoma cells. Infection of DCs with parental VZV resulted in a different pattern of phosphoproteins compared with the ORF47 mutant virus. Thus, VZV ORF47 is important for replication in immature DCs and for spread to other cells. 相似文献
2.
The ORF II protein (PII) of Soybean chlorotic mottle virus (SbCMV) is essential for the virus life cycle. We investigated the interactions of SbCMV PII with itself and with other essential virus proteins using a Gal4-based yeast two-hybrid system. PII interacted only with itself and not with any other virus proteins. The PII-PII interaction was confirmed by a Sos-based yeast two-hybrid system and a far-western analysis. Deletion mutagenesis mapped the self-interacting domain to the C-terminal 48 amino acids (amino acids 154-201), which contain two putative leucine zipper motifs. Introduction of amino acid substitutions to leucine/isoleucine in zipper sequences prevented the PII-PII interaction and abolished the infectivity of SbCMV. These results revealed that the self-interaction of PII through a leucine zipper is necessary for virus infection. 相似文献
3.
Retroviral resistance mediated by the murine Fv1 gene is believed to result from a direct interaction between the Fv1 gene product and the viral capsid protein. To study the mechanism of Fv1 action, the expression and intracellular localisation of the Fv1 protein were examined. Only very low levels of protein expression seem necessary for virus restriction but the site of expression appears crucial. Active Fv1 was found in association with tubules of the trans-Golgi network, whereas an inactive form was localised in the endoplasmic reticulum. We hypothesize that Fv1 is compartmentalised in the cell on the pathway taken by virus en route to the nucleus, suggesting that incoming virus must pass the trans-Golgi network during its transit to the nucleus. 相似文献
4.
Background
During the viremic phase of human immunodeficiency virus type-1 (HIV-1) infection, hepatocytes are likely to be constantly exposed to circulating virions. Knowing that a contact between hepatocytes and CD4+ T lymphocytes is favoured by the local slow blood flow present within the liver, we hypothesize that hepatic cells can act as a viral reservoir and thus contribute to HIV-1 propagation.Results
We report that human hepatoma cells bind and internalize HIV-1 particles. Infection of CD4+ T cells was found to be much more efficient following a contact with virus-loaded hepatocytes than with cell-free virus. Additional studies suggest that infection of CD4+ T cells in trans with hepatocytes carrying virus is primarily due to surface bound HIV-1 particles and relies on LFA-1/ICAM-1 interactions.Conclusion
This work represents the first demonstration by which circulating CD4+ T cells can be potentially infected with HIV-1 through a contact with hepatocytes in the liver. 相似文献5.
Nakataki M Iga J Numata S Yoshimoto E Kodera K Watanabe SY Song H Ueno S Ohmori T 《Neuroscience letters》2011,489(2):126-130
The epithelial membrane protein 1 (EMP1) plays a role in neuronal differentiation and neurite outgrowth, which are involved in the pathogenesis of major depressive disorder (MDD). We sought to determine whether the EMP1 gene is implicated in MDD. We determined the mRNA expression levels of the EMP1 gene in peripheral-blood leukocytes of patients and control subjects (n=27 each). Next, we performed case-control association analyses (MDD, n=182; controls, n=350) in the Japanese population. The level of expression of the EMP1 mRNA was significantly lower in medication-free patients compared with control subjects (P<0.001). The association analysis revealed an absence of association between the polymorphisms studied and MDD, whereas a gender-specific association was observed between male controls and male patients for marker rs7315725 (permutation P=0.039). Our results suggest that the EMP1 gene may be implicated in the pathophysiology of MDD in the Japanese population. 相似文献
6.
Gianfrancesco F Esposito T Penco S Maglione V Liquori CL Patrosso MC Zuffardi O Ciccodicola A Marchuk DA Squitieri F 《Neuroscience》2008,155(2):345-349
The past few years have seen rapid advances in our understanding of the genetics and molecular biology of cerebral cavernous malformations (CCM) with the identification of the CCM1, CCM2, and CCM3 genes. Recently, we have recruited a patient with an X/3 balanced translocation that exhibits CCM. By fluorescent in situ hybridization analysis, sequence analysis tools and database mining procedures, we refined the critical region to an interval of 200-kb and identified the interrupted ZPLD1 gene. We detected that the mRNA expression level of ZPLD1 gene is consistently decreased 2.5-fold versus control (P=0.0006) with allelic loss of gene expression suggesting that this protein may be part of the complex signaling pathway implicated in CCM formation. 相似文献
7.
Yingchao Nie 《Virology》2010,404(2):168-179
This study investigated the combined function of the Autographa californica multiple nucleopolyhedrovirus overlapping genes ac16 (BV/ODV-E26, DA26) and ac17. Ac17 is a late gene and the promoter is within the ac16 open reading frame. A double ac16-ac17 knockout virus was generated to assess the function of each gene independently or together. Loss of ac17 did not affect viral DNA synthesis but budded virus (BV) production was reduced. Deletion of both ac16-ac17 resulted in reduced viral DNA synthesis and a further reduction in BV production. In BV infected Sf9 cells, viral gene expression was delayed up to 12 h in the absence of both AC16 and AC17 but not if either gene was present. Cells infected by transfecting viral DNA, by-passing the BV particle, exhibited no delay in gene expression from the double knockout virus. AC16 and AC17 are therefore required for rapid viral gene expression in cells infected by BV. 相似文献
8.
Enterobacter sakazakii (ES) causes neonatal meningitis and necrotizing enterocolitis with case-fatality rates among infected infants ranging from 40 to 80%. Very little is known about the mechanisms by which these organisms cause disease. Here, we demonstrate that ES invades human brain microvascular endothelial cells (HBMEC) with higher frequency when compared with epithelial cells and endothelial cells from different origins. The entry of ES into HBMEC requires the expression of outer membrane protein A (OmpA), as the OmpA-deletion mutant was sevenfold less invasive than the wild type ES and the bacterium does not multiply inside HBMEC. Anti-OmpA antibodies generated against the OmpA of Escherichia coli K1, which also recognize the OmpA of ES, did not prevent the invasion of ES in HBMEC. ES invasion depends on microtubule condensation in HBMEC and is independent of actin filament reorganization. Both PI3-kinase and PKC-alpha were activated during ES entry into HBMEC between 15min and 30min of infection. Concomitantly, overexpression of dominant negative forms of PI3-kinase and PKC-alpha significantly inhibited the invasion of ES into HBMEC. In summary, ES invasion of HBMEC is dependent on the expression of OmpA similar to that of E. coli K1; however, the epitopes involved in the interaction with HBMEC appears to be different. 相似文献
9.
10.
Afagh Alavi Shahriar Nafissi Mohammad Rohani Gholamali Shahidi Babak Zamani Hosein Shamshiri Iman Safari Elahe Elahi 《Neurobiology of aging》2014
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in populations of European descent. It was recently found that a hexanucleotide repeat expansion in C9ORF72 is its most common cause in these populations. The contribution of C9ORF72 to ALS is notably lower in the Far East, but its role in other populations is unknown. Results of C9ORF72 screening in 78 unrelated Iranian ALS patients are reported here. The repeat expansion was observed in only 1 (5.9%) of the familial and 1 (1.6%) of the sporadic cases. These figures are to be compared, respectively, with 30% and 6.9% among patients of European ethnicity. Screenings of C9ORF72 in other Middle East countries will reveal whether the low contribution of C9ORF72 to ALS is a feature of the entire region. During the screenings, it was noted that in a single family, 3 individuals affected with ALS, Parkinson's disease, or frontotemporal dementia all carried the repeat expansion. The finding suggests the mutation does rarely contribute to the etiology of Parkinson's disease. 相似文献
11.
Suppression of porcine reproductive and respiratory syndrome virus replication in MARC-145 cells by shRNA targeting ORF1 region 总被引:2,自引:0,他引:2
Porcine reproductive and respiratory syndrome (PRRS) is an economically important disease in swine producing area. The current
vaccine strategies cannot provide complete protection against PRRSV. The objective of this study was to determine if specific
short-hairpin RNA (shRNA) directed against different genomic regions of ORF1b of PRRSV could be utilized to inhibit virus
replication in MARC-145 cells. Two shRNA expression vectors targeting ORF1b gene of PRRSV were constructed and delivered into
MARC-145 cells, and then infected with PRRSV. The results showed that PRRSV-specific cytopathic effect (CPE) could be inhibited
in the cells transfected with pSUPER-P2 and pSUPER-P3, and the virus titers in the cells transfected with pSUPER-P2 and pSUPER-P3
were lower than those control cells by approximately 100 fold. Moreover, the expression of ORF1 of PRRSV in the cells was
reduced both at RNA and protein levels comparing to the controls. It indicated that vector-based shRNA targeting ORF1 region
could effectively inhibit PRRSV replication in MARC-145 cells.
Guanming Li and Juan Huang contributed equally to this work. 相似文献
12.
We have identified the gene product of locus 766 in the transmembrane head region (TMH/Inc-region) in the Chlamydophila abortus genome by using mass spectrometry and a monoclonal antibody that reacted with the inclusion membrane. The identified protein at 32kDa, termed Inc766, formed highly stable oligomers when solubilized in the absence of beta-mercaptoethanol. These oligomers were resistant to SDS, to heat denaturation and to 8M urea, but very sensitive to beta-mercaptoethanol, consistent with conformations resulting from protein-protein interactions stabilized through disulphide bonds. Mass spectrometry analysis of immunoprecipitated infected cell lysates indicated that a dimer at 56kDa was the most prominent form in solution. Cross-linking with DSP provided supporting evidence for the formation of oligomers in situ. Inc766 was expressed at 20-24h post infection and its localization pattern in the extra-inclusion space was common in all C. abortus strains tested. Taken together, Inc766 displays unique biochemical and cellular features not encountered in other Incs from other Chlamydiaceae species. Future studies of the particular characteristics especially the interactive properties of Inc766 should contribute to our understanding of the relationship of the different chlamydial species with their respective hosts. 相似文献
13.
Mónica Mendoza-Rodriguez Hugo Arreola Alejandra Valdivia Raúl Peralta Humberto Serna Vanessa Villegas Pablo Romero Beatriz Alvarado-Hernández Lucero Paniagua Daniel Marrero-Rodríguez Marco A Meraz Mauricio Salcedo 《International journal of clinical and experimental pathology》2013,6(9):1817-1825
Aims: Cervical Cancer (CC) is one of the most important health problems in women. It frequently presents genetic changes at chromosome region 3q21. This region contains the Cellular Retinol Binding Protein 1 gene (CRBP1) which has been implicated as an important element in the development of other types of cancer. The main goal of the present work was to determine the molecular alterations of CRBP1 and its relationship to CC. Methods: To determine the molecular alterations of CRBP1 gene in CC; twenty-six CC and twenty-six healthy cervix samples were evaluated for: 1) Copy number gain by real-time PCR analysis, 2) expression levels by an immunohistochemistry assay on tissue microarray, and 3) the methylation status of the CRBP1 promoter region. Results: The increase in CRBP1 copy number was observed in 10 out of the 26 CC samples analyzed, while healthy cervices samples showed no changes in the copy number. In addition, there was a lack of expression of the CRBP1 gene in an important number of the CC samples (17/26), and the CRBP1 gene promoter was methylated in 15/26 of the CC samples. Interestingly, there was a significant association between the lack of expression of the CRBP1 gene and its methylation status. Conclusions: The data indicates that, both activating and inactivating changes in the CRBP1 gene could be significant events in the development and progression of CC, and the lack of expression of the CRBP1 protein could be related with to the development of CC. We believe that there is enough evidence to consider to CRBP1 gene as a tumor suppressor gene for CC. 相似文献
14.
The discovery of LRRK2 gene mutations in late-onset Parkinson's disease (PD) has irrevocably established the role of genetics in the etiology of PD. The LRRK1 gene is the single homolog of LRRK2. A high degree of homology exists between LRRK1 and LRRK2, indicative of shared functions and/or pathways. One study has examined LRRK1 in familial parkinsonism by complete sequencing of the gene, reporting 4 novel non-synonymous coding variants within the LRRK1 gene. One of these variants (ss65713826) was identified in a Norwegian proband. We investigated whether five common polymorphisms or these recently identified coding changes within LRRK1 are associated with PD in the Norwegian population. Two rare coding variants ss65713826 and ss65713830 were more frequent in patients than controls. However, their identification in healthy controls and lack of co-segregation with disease suggests they may represent benign polymorphisms. 相似文献
15.
The entirevpr gene of human immunodeficiency virus type 1 (HIV-1) was cloned into procaryotic and eucaryotic expression vectors. Production of authentic protein encoded by the gene in bacterial and mammalian cells was monitored by Western blotting using guinea pig antisera raised against an N-terminal 14-oligopeptide of the predictedvpr protein. A specific 12-kD protein was clearly detected with these antisera, but not with preimmune sera, in both cell systems, and this binding was blocked by the oligopeptide. These antisera also recognized a protein of the same size in several human T-cell lines infected with HIV-1. Western blotting analysis of subcellular fractions prepared from the cells producing wildtypevpr protein strongly suggested that the protein was membrane associated. A region within thevpr required for the stable expression ofvpr product was also suggested by mutational analyses. 相似文献
16.
Herholz J Meloni A Marongiu M Chiappe F Deiana M Herrero CR Zampino G Hamamy H Zalloum Y Waaler PE Crisponi G Crisponi L Rutsch F 《European journal of human genetics : EJHG》2011,19(5):525-533
Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) are disorders caused by mutations in CRLF1. The two syndromes share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia, associated with death in most cases in the first years of life. To evaluate a potential genotype/phenotype correlation and whether CS and CISS1 represent two allelic diseases or manifestations at different ages of the same disorder, we carried out a detailed clinical analysis of 19 patients carrying mutations in CRLF1. We studied the functional significance of the mutations found in CRLF1, providing evidence that phenotypic severity of the two disorders mainly depends on altered kinetics of secretion of the mutated CRLF1 protein. On the basis of these findings, we believe that the two syndromes, CS and CISS1, represent manifestations of the same disorder, with different degrees of severity. We suggest renaming the two genetic entities CS and CISS1 with the broader term of Sohar-Crisponi syndrome. 相似文献
17.
目的: 探讨EB病毒潜伏性膜蛋白 1(LMP1)促鼻咽上皮细胞增殖的分子机制。方法: 采用逆病毒感染的方法,将浓缩的逆病毒RV-pLNSX(空载体)和RV-LMP1分别感染鼻咽上皮细胞NP69,建立NP69-pLNSX与NP69-LMP1稳定表达细胞系,通过绘制细胞生长曲线、平皿克隆形成实验和软琼脂集落形成实验检测LMP1对NP69细胞增殖的影响;运用比较蛋白质组学方法鉴定LMP1在NP69细胞中参与调节的蛋白,并对部分蛋白表达进行验证。结果: (1) LMP1具有促鼻咽上皮细胞NP69增殖的作用(n=3,P<0.05)。(2) 鉴定了22个LMP1参与调节NP69细胞的蛋白(表达上调的蛋白9个,下调的13个),实时荧光定量RT-PCR和Western blotting证实了部分上述蛋白的差异表达。结论: LMP1可能通过参与调节keratin 19和vimentin等蛋白的表达促鼻咽上皮细胞NP69增殖。 相似文献
18.
Chen Z Tang NL Cao X Qiao D Yi L Cheng JC Qiu Y 《European journal of human genetics : EJHG》2009,17(4):525-532
Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P=0.0007, odds ratio (OR)=1.35 within 95% confidence interval (CI)=1.14-1.61), and individuals with genotype GG had a higher risk for AIS compared with AA+AG (P=0.0001, OR=1.61 within 95% CI=1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P=0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS. 相似文献
19.
Osada R Horiuchi A Kikuchi N Yoshida J Hayashi A Ota M Katsuyama Y Melillo G Mellilo G Konishi I 《Human pathology》2007,38(9):1310-1320
20.
Ronen Spiegel Ann Saada Jonatan Halvardson Devorah Soiferman Avraham Shaag Simon Edvardson Yoseph Horovitz Morad Khayat Stavit A Shalev Lars Feuk Orly Elpeleg 《European journal of human genetics : EJHG》2014,22(7):902-906
Isolated metabolic myopathies encompass a heterogeneous group of disorders, with mitochondrial myopathies being a subgroup, with depleted skeletal muscle energy production manifesting either by recurrent episodes of myoglobinuria or progressive muscle weakness. In this study, we investigated the genetic cause of a patient from a consanguineous family who presented with adolescent onset autosomal recessive mitochondrial myopathy. Analysis of enzyme activities of the five respiratory chain complexes in our patients'' skeletal muscle showed severely impaired activities of iron sulfur (Fe-S)-dependent complexes I, II and III and mitochondrial aconitase. We employed exome sequencing combined with homozygosity mapping to identify a homozygous mutation, c.1A>T, in the FDX1L gene, which encodes the mitochondrial ferredoxin 2 (Fdx2) protein. The mutation disrupts the ATG initiation translation site resulting in severe reduction of Fdx2 content in the patient muscle and fibroblasts mitochondria. Fdx2 is the second component of the Fe-S cluster biogenesis machinery, the first being IscU that is associated with isolated mitochondrial myopathy. We suggest adding genetic analysis of FDX1L in cases of mitochondrial myopathy especially when associated with reduced activity of the respiratory chain complexes I, II and III. 相似文献