Shi Y.,CAS Institute of Microbiology |
Shi Y.,Shenzhen Third Peoples Hospital |
Shi Y.,Chinese Academy of Sciences |
Shi Y.,University of Chinese Academy of Sciences |
And 5 more authors.
Trends in Biochemical Sciences | Year: 2017
Zika virus (ZIKV), a Flaviviridae family member transmitted to humans by mosquitoes, has emerged as a major health concern. ZIKV infections can cause serious neurological complications in adults, and infection in pregnant women can cause congenital malformations, including fetal and newborn microcephaly. In response to this emerging concern, the structural virology field was quick to explore the features of ZIKV. These efforts have provided significant insights into ZIKV pathogenesis, and have identified targets for drug design. Here, we review the remarkable progress in structure-based ZIKV research and discuss the current challenges and future opportunities. Cryo-electron microscopy (EM) structural studies revealed that the ZIKV particle has two unique features: a protruding N154 glycosylation site and a more compact surface with higher thermostability. Moreover, the immature ZIKV contains a partially ordered capsid protein shell, which is lacking in the mature ZIKV particle, suggesting a rearrangement of capsid shell during maturation.Both flavivirus E-cross-reactive and ZIKV E-specific neutralizing antibodies confer protection against ZIKV infection in a mouse model, and structural analysis showed that these antibodies bind to different regions on the E protein.Analysis of the structure of the full-length ZIKV NS1 identified a new membrane-association site in the wing domain, and unique characteristics of its outer surface.Analysis of the structures of ZIKV NS3 and NS5 revealed conserved features that will aid in the structure-based design of antiviral compounds against ZIKV. © 2017 Elsevier Ltd.
Xiao J.,Jinan University |
Xiao J.,Shenzhen Third Peoples Hospital |
Xiao J.,University of Hong Kong |
Tipoe G.L.,University of Hong Kong
Frontiers in Bioscience - Landmark | Year: 2016
Non-alcoholic fatty liver disease (NAFLD) is a leading liver disorder in the world. Inflammation is one of the most important pathological events during the development of NAFLD and also represents the hallmark between simple steatosis and non-alcoholic steatohepatitis (NASH). Inflammasomes are novel protein complex platforms assembled in response to patternassociated molecular patterns (PAMPs) and damageassociated molecular patterns (DAMPs). Currently, there are several identified inflammasomes, including nod-like receptor protein (NLRP)-1, 2, 3, 6, 10, 12, NLRC4 and absent in melanoma 2 (AIM2) inflammasomes. In the liver, inflammasomes are primarily expressed in immune cells. However, increasing evidence suggests that their expressions in other types of cells in the liver are also present. In general, inflammasomes are up-regulated in various liver diseases. In NAFLD, it is reported that the levels of inflammasome components (e.g. NLRPs, caspase-1, IL-1β and IL-18) are elevated. Silence of these components attenuates hepatic injury. Collectively, the main purposes of this review are to examine the recent progress of hepatic inflammasome research and to discuss possible directions of therapeutic strategy and development against NAFLD.
Lam T.T.-Y.,Shenzhen Third Peoples Hospital |
Lam T.T.-Y.,Shantou University |
Lam T.T.-Y.,University of Hong Kong |
Zhou B.,Shenzhen Third Peoples Hospital |
And 34 more authors.
Nature | Year: 2015
Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013 (refs 3, 4, 5, 6, 7). It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses. © 2015 Macmillan Publishers Limited. All rights reserved.
Lau R.W.T.,University of Hong Kong |
Ho P.-L.,University of Hong Kong |
Kao R.Y.T.,University of Hong Kong |
Yew W.-W.,Grantham Hospital |
And 6 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011
A PCR-sequencing assay was evaluated for direct detection of mutations in the quinolone resistance-determining region (QRDR) of gyrase A (gyrA) gene in fluoroquinolone-resistant Mycobacterium tuberculosis in respiratory specimens. As determined by gyrA QRDR analysis, complete concordance of genotypic and phenotypic fluoroquinolone resistance was demonstrated. Our results indicate that the assay is a rapid and reliable method for the diagnosis of fluoroquinolone-resistant tuberculosis, facilitating timely clinical management and public health control. Using the assay, we detected a novel gyrA Ala74Ser mutation in M. tuberculosis directly from sputum specimens. The functional effect of the Ala74Ser mutant was verified through the study of the DNA supercoiling inhibitory activity of fluoroquinolones against the recombinant gyrase. The drug-mediated gyrase-DNA cleavage complex model suggests perturbation of the gyrA-gyrA dimer interface caused by the Ala74Ser mutation probably disturbs the putative quinolone binding pocket and leads to the reduction of the drug binding affinity. A number of gyrA mutations (Glu21Gln, Ser95Thr, and Gly668Asp) were also characterized to be natural polymorphisms not associated with fluoroquinolone resistance. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Jones J.C.,St Jude Childrens Research Hospital |
Baranovich T.,St Jude Childrens Research Hospital |
Zaraket H.,St Jude Childrens Research Hospital |
Guan Y.,University of Hong Kong |
And 4 more authors.
Journal of Virology | Year: 2013
Recently, novel H7N9 influenza viruses have caused an unprecedented outbreak in humans. Pigs are an important intermediate host for influenza; thus, we assessed the replication ability of three human H7N9 viruses (A/Anhui/1/2013, A/Shanghai/1/2013, A/Shanghai/2/2013) in swine tissue explants. All viruses tested replicated efficiently in explants from tracheas and bronchi, with limited replication in alveolar cells. Swine respiratory tissue explants can serve as an efficient model for screening replication potential of newly emerging H7N9 viruses. © 2013, American Society for Microbiology.
Wang Y.-X.J.,Interventional Imaging |
Yuan J.,Interventional Imaging |
Chu E.S.H.,Chinese University of Hong Kong |
Go M.Y.Y.,Chinese University of Hong Kong |
And 5 more authors.
Radiology | Year: 2011
Purpose: To correlate spin-lattice relaxation time in the rotating frame (T1ρ) measurements with degree of liver fibrosis in a rat model. Materials and Methods: The protocols and procedures were approved by the local Animal Experimentation Ethics Committee. Liver fibrosis was induced with biliary duct ligation (BDL). Two studies, 1 month apart, were performed with a 3-T clinical imager. The first study involved longitudinal magnetic resonance (MR) imaging follow-up of BDL rats (n = 8) and control rats (n = 4) on days 8, 15, 21, and 29 after BDL. The second study involved MR imaging of another group of BDL and control rats (n = 5 for each) on days 24 and 38 after BDL. Hematoxylin-eosin and picrosirius red staining were performed in liver specimens from days 8, 15, 24, and 38 after BDL. Repeated-measures analysis of variance was used, and treatment groups were compared (Bonferroni adjustment). Results: On day 8, there were proliferation of bile duct and inflammatory cell infiltration around portal triads. While there was overlap, BDL rats (n = 8) demonstrated higher mean liver T1ρ values than did control rats(n = 4) on day 8 (46.7 msec ± 2.9 [standard deviation] vs 44.7 msec ± 1.2, P =.4). On day 15, BDL rats demonstrated liver fibrosis with a background of inflammatory infiltration. On day 15, mean T1ρ values in BDL rats could be largely separated from those in control rats (52.6 msec ± 6.0 vs 43.8 msec ± 1.5, P =.02). On day 24, BDL rats had liver T1ρ values 23.5% higher than in control rats (n = 5 for each group, P =.0007). Histomorphometric analysis showed that collagen content increased after surgery from days 8 to 24 (n = 6 for each group, P<.0001), with no further increase between days 24 and 38 (n = 6 for each group, P>.99). Conclusion: In this model, liver fibrosis was detected with T1ρ MR imaging; the degree of fibrosis was correlated with degree of increase in T1ρ measurements. © RSNA, 2011.
Kovacs J.R.,University of Pittsburgh |
Li C.,University of Pittsburgh |
Yang Q.,University of Pittsburgh |
Yang Q.,Shenzhen Third Peoples Hospital |
And 9 more authors.
Cell Death and Differentiation | Year: 2012
Autophagy is implicated in regulating cell death in activated T cells, but the underlying mechanism is unclear. Here, we show that inhibition of autophagy via Beclin 1 gene deletion in T cells leads to rampant apoptosis in these cells upon TCR stimulation. Beclin 1-deficient mice fail to mount autoreactive T-cell responses and are resistant to experimental autoimmune encephalomyelitis. Compared with Th17 cells, Th1 cells are much more susceptible to cell death upon Beclin 1 deletion. Cell death proteins are highly increased in Beclin 1-deficient T cells and inhibition of caspases and genetic deletion of Bim reverse apoptosis. In addition, p62/sequestosome 1 binds to caspase-8 but does not control levels of procaspase-8 or other cell death-related proteins. These results establish a direct role of autophagy in inhibiting the programmed cell death through degradation of apoptosis proteins in activated T cells. © 2012 Macmillan Publishers Limited All rights reserved.
Gao X.,Soochow University of China |
Zhu Y.,Soochow University of China |
Zhu Y.,University of Pittsburgh |
Li G.,Soochow University of China |
And 7 more authors.
PLoS ONE | Year: 2012
Background: T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8 + T cells in both chronic infection and tumor. However, the nature of TIM-3 +CD4 + T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression. Methodology: A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters. Conclusions: TIM-3 is highly upregulated on both CD4 + and CD8 + TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ + cells were reduced in TIM-3 +CD8 + TILs compared to TIM-3 -CD8 + TILs. However, the level of TIM-3 expression on CD8 + TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3 +CD4 + TILs expressed FOXP3 and about 60% of FOXP3 + TILs were TIM-3 +. Importantly, TIM-3 expression on CD4 + T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells. © 2012 Gao et al.
Lu P.X.,Shenzhen Third Peoples Hospital
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases | Year: 2010
To evaluate the value of chest CT findings and dynamic changes of viral load in patients with novel influenza A (H1N1) infection in clinical diagnosis, differential diagnosis and treatment. Fifty-one patients with confirmed novel influenza A (H1N1) according to the diagnostic criteria of the Ministry of Health, received chest X-ray, CT scans (HRCT) and viral load tests in our hospital from May to December of 2009. Based on whether there were signs of pneumonia in CT imaging, the patients were divided into a pneumonia group (n = 31) and a non-pneumonia group (n = 20). The relationship between chest CT changes and viral load was observed and analyzed statistically using SPSS 10.5 software. Patchy consolidations of lungs were the main findings in pneumonia group with influenza A (H1N1) infection, and ground-glass opacities were the main CT findings at acute and convalescent phases. Lobular and segmental shadows of the lungs were diffusely distributed, mostly found in lower lungs, especially the left lung. In some cases, the lung diseases were accompanied with mediastinal lymphadenopathy. Co-existence of pulmonary parenchymal, interstitial and pleural diseases was observed. Peak viral load occurred at the early phase of illness, with the mean initial viral load being 7.7 copies/ml and 4.2 copies/ml in the pneumonia and the non-pneumonia groups respectively. The viral nucleic acid became negative 4 days after antiviral treatment (course of 6 days). Dynamic observation of 3 patients with novel influenza A (H1N1) pneumonia showed that, the viral clearance period preceded the absorption of lung lesions in 2 cases, but viral clearance period of a young patient was significantly prolonged. In patients with the novel influenza A (H1N1) infection, the viral load in the pneumonia group was significantly higher than that in the group with normal chest imaging. Dynamic observation on chest imaging and viral load may be beneficial for clinicians to start prompt and effective treatment.
Yue J.R.,Shenzhen Third Peoples Hospital
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology | Year: 2013
To assess healthy related quality of life in patients with HBV induced liver cirrhosis. A total of 103 cases of patients with HBV induced liver cirrhosis were recruited from shenzhen Third People's Hospital during January 2009 to January 2012. The health related quality of life were assess using the most commonly used SF-36 scale questionnaire in all 103 patiemts. Sixty patients were further chosen for health related quality assessment using qualitive research method. The quality of life of chronic hepatitis B patients with cirrhosis Child classification, four score of each group general health, vitality, social functioning, mental health was statistically significant (P < 0.05). Depth interviews found that the disease affects the psychological burden of the social needs of the three major affect quality of life factors. Qualitative research with the SF-36 scale associated to a better understanding of the needs of life of patients with chronic hepatitis B cirrhosis, provide a reference for subsequent targeted medical services.