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Endosomes and Microtubles are Required for Productive Infection in Aquareovirus

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Virologica Sinica 2020年第2期35卷 200-211页

作者： Fuxian Zhang Hong Guo Qingxiu Chen Zheng Ruan Qin Fang State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of Sciences.Wuhan 430071China Wuhan Center for Animal Diseases Prevention and Control Wuhan 430071China

Grass carp reovirus(GCRV),the genus Aquareovirus in family Reoviridae,is viewed as the most pathogenic *** understand the molecular mechanism of how aquareovirus initiates productive infection,the roles of endosome and microtubule in cell entry of GCRV are investigated by using quantum dots(QDs)-tracking in combination with biochemical *** found that GCRV infection and viral protein synthesis were significantly inhibited by pretreating host cells with endosome acidification inhibitors NH4Cl,chloroquine and bafilomycin A1(Bafi).Confocal images indicated that GCRV particles could colocalize with Rab5,Rab7 and lysosomes in host *** ultrastructural examination validated that viral particle was found in late ***,disruption of microtubules with nocodazole clearly blocked GCRV entry,while no inhibitory effects were observed with cytochalasin D treated cells in viral infection,hinting that intracellular transportation of endocytic uptake in GCRV infected cells is via microtubules but not actin ***,viral particles were observed to transport along microtubules by using QD-labeled ***,our results suggest that GCRV can use endosomes and microtubules to initiate productive infection.

关键词： Aquareovirus cell entry Quantum dot Endosome Microtubule

Targeting host factors:A novel rationale for the management of hepatitis C virus

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World Journal of Gastroenterology 2009年第28期15卷 3472-3479页

作者： Mahmoud Aboelneen Khattab Department of Internal Medicine El-Minia University

Hepatitis C is recognized as a major threat to global public health. The current treatment of patients with chronic hepatitis C is the addition of ribavirin to interferon-based therapy which has limited efficacy, poor tolerability, and significant expense. New treatment options that are more potent and less toxic are much needed. Moreover, more effective treatment is an urgent priority for those who relapse or do not respond to current regimens. A major obstacle in combating hepatitis C virus （HCV） infection is that the fidelity of the viral replication machinery is notoriously low, thus enabling the virus to quickly develop mutations that resist compounds targeting viral enzymes. Therefore, an approach targeting the host cofactors, which are indispensable for the propagation of viruses, may be an ideal target for the development of antiviral agents because they have a lower rate of mutation than that of the viral genome, as long as they have no side effects to patients. Drugs targeting, for example, receptors of viral entry, host metabolism or nuclear receptors, which are factors required to complete the HCV life cycle, may be more effective in combating the viral infection. Targeting host cofactors of the HCV life cycle is an attractive concept because it imposes a higher genetic barrier for resistance than direct antiviral compounds. However the principle drawback of this strategy is the greater potential for cellular toxicity.

关键词： Host factors Hepatitis C virus Noveltreatment cell entry Host metabolism Nuclearreceptors Insulin resistance

High-resolution 3D Structures Reveal the Biological Functions of Reoviruses

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Virologica Sinica 2013年第6期28卷 318-325页

作者： Xiaoming Li Qin Fang State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of Sciences School of Basic Medical Sciences Wuhan University

Viruses in the family Reoviridae are non-enveloped particles comprising a segmented double-stranded RNA genome surrounded by a two-layered or multi-layered icosahedral protein *** viruses are classified into two sub-families based on their particle structural *** studies have focused on high-resolution three-dimensional structures of reovirus particles by using cryo-electron microscopy (cryo-EM) to approach the resolutions seen in X-ray crystallographic *** results of cryo-EM image reconstructions allow tracing of most of the protein side chains,and thus permit integration of structural and functional information into a coherent mechanism for reovirus assembly and entry.

关键词： Non-enveloped virus Reoviruses Structural basis Assembly cell entry

COVID-19 and Chronic Viral Liver Diseases

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Journal of Biosciences and Medicines 2021年第9期9卷 138-146页

作者： Maged Tharwat Elghannam Motaz Hasan Hassanien Yosry Abdelrahman Gamalaldin Mohammed ALattar Emad Abdelwahab Turky Ahmed Aly EL Ray Mohammed Darwish EL Talkawy Hepatogastroenterology Department Theodor Bilharz Research Institute EL Warak Giza Egypt

Coronavirus causes an outbreak of viral pneumonia that spread throughout the world. Liver injury is becoming more widely recognized as a component of the clinical picture of COVID-19 infection. We aimed to review this relation in a concise way. This review article includes a large number of patients from both western and eastern countries with no clear difference of liver affection. The more severe and frequent liver injury, the more severe COVID-19 infection. Up to half of patients developed hepatitis with serum ALT elevation. Both hepatocellular and/or ductular injury were observed as evidenced by alkaline phosphatase elevation. Increase incidence of morbidity and mortality had been recorded in patients with CLD. Cirrhosis mortality extended in line with the Child-Turcotte-Pugh class. The incidence of ACLF in CLD patients with COVID 19 is not clear. There are no significant associations with the etiology of liver disease and death in cirrhosis. COVID-19 hinders HCV elimination by 2030. Patients should continue their medications if already receiving treatment. Patients with occult or resolved HBV and COVID-19 who are receiving immunosuppressive agents should use antiviral therapy to prevent viral flare-ups.

关键词： COVID-19 Chronic Liver Disease cell entry Pathology Pathogenesis and Pathophysiology Impact on CLD

Single virus tracking of Ebola virus entry through lipid rafts in living host cells

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Biosafety and Health 2020年第1期2卷 25-31页

作者： Jin Cong Che Bin Guo Zhengyuan Li Chuan Liu Yang Wu Wei Wang Shiwen Li Dexin Cui Zongqiang Liang Mifang Key Laboratory of Medical Virology and Viral Diseases Ministry of Health of People's Republic of ChinaNational Institute for Viral Disease Control and Prevention(IVDC)Chinese Center for Disease control and Prevention(China CDC)Beijing 102206China National Center for AIDS/STD Control and Prevention China CDCBeijing 102206China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China Center for Biosafety Mega-Science Chinese Academy of SciencesBeijing 100049China

Ebola virus(EBOV)is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic *** the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and *** has been known that EBOV virions bind to factors expressed at the host cell ***,the virions are internalized by a macropinocytosis-like process,followed by being trafficked through early and late *** researches indicate that the entry of EBOV into cells requires integrated and functional lipid *** lipid rafts have been hypothesized to play a role in virus entry,there is a current lack of supporting *** major technical hurdle is the lack of effective approaches for observing viral *** provide evidence on the involvement of lipid rafts in the entry process of EBOV,we generated the fluorescently labeled Ebola virus like particles(VLPs),and utilized single-particle tracking(SPT)to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid *** this study,we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process,and inform the essential function of lipid rafts for the entry of Ebola *** such,our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.

关键词： Ebola viruses Single particle tracking Lipid raft cell entry Pathogenesis