LIVIVO - Search results -

Search results

Result 1 - 10 of total 19

Search options

Article ; Online: Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles

Yun Lan / Sophie Wilhelmina van Leur / Julia Ayano Fernando / Ho Him Wong / Martin Kampmann / Lewis Siu / Jingshu Zhang / Mingyuan Li / John M. Nicholls / Sumana Sanyal

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract Infection by many (+)RNA viruses is accompanied by ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus-triggered lipophagy was ... ...

Abstract	Abstract Infection by many (+)RNA viruses is accompanied by ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus-triggered lipophagy was critical for flaviviral assembly, and is driven by the lipid droplet associated protein Ancient ubiquitin protein 1 (Aup1). A ubiquitin conjugating protein Ube2g2 that functions as a co-factor for Aup1 was identified as a host dependency factor in our study. Here we characterized its function: Ube2g2-deficient cells displayed a dramatic reduction in virus production, which could be rescued by reconstituting the wild-type but not the catalytically deficient (C89K) mutant of Ube2g2, suggesting that its enzymatic activity is necessary. Ube2g2 deficiency did not affect entry of virus particles but resulted in a profound loss in formation of replication organelles, and production of infectious progenies. This phenomenon resulted from its dual activity in (i) triggering lipophagy in conjunction with Aup1, and (ii) degradation of ER chaperones such as Herpud1, SEL1L, Hrd1, along with Sec62 to restrict ER-phagy upon Xbp1-IRE1 triggered ER expansion. Our results therefore underscore an exquisite fine-tuning of selective autophagy by flaviviruses that drive host membrane reorganization during infection to enable biogenesis of viral replication organelles.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Replication of Novel Zoonotic-Like Influenza A(H3N8) Virus in Ex Vivo Human Bronchus and Lung

Kenrie P.Y. Hui / John C.W. Ho / Ka-Chun Ng / Samuel M.S. Cheng / Ko-Yung Sit / Timmy W.K. Au / Leo L.M. Poon / John M. Nicholls / Malik Peiris / Michael C.W. Chan

Emerging Infectious Diseases, Vol 29, Iss 6, Pp 1210-

2023 Volume 1214

Abstract: Human infection with avian influenza A(H3N8) virus is uncommon but can lead to acute respiratory distress syndrome. In explant cultures of the human bronchus and lung, novel H3N8 virus showed limited replication efficiency in bronchial and lung tissue ... ...

Abstract	Human infection with avian influenza A(H3N8) virus is uncommon but can lead to acute respiratory distress syndrome. In explant cultures of the human bronchus and lung, novel H3N8 virus showed limited replication efficiency in bronchial and lung tissue but had a higher replication than avian H3N8 virus in lung tissue.
Keywords	influenza ; H3N8 ; risk assessment ; human bronchus ; human lung ; influenza A virus ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Risk Assessment for Highly Pathogenic Avian Influenza A(H5N6/H5N8) Clade 2.3.4.4 Viruses

Christine H.T. Bui / Denise I.T. Kuok / Hin Wo Yeung / Ka-Chun Ng / Daniel K.W. Chu / Richard J. Webby / John M. Nicholls / J.S. Malik Peiris / Kenrie P.Y. Hui / Michael C.W. Chan

Emerging Infectious Diseases, Vol 27, Iss 10, Pp 2619-

2021 Volume 2627

Abstract: The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. We investigated the tropism and innate host responses of 5 recent ... ...

Abstract	The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. We investigated the tropism and innate host responses of 5 recent HPAI A(H5N6/H5N8) avian isolates of clades 2.3.4.4b, e, and h in human airway organoids and primary human alveolar epithelial cells. The HPAI A(H5N6/H5N8) avian isolates replicated productively but with lower competence than the influenza A(H1N1)pdm09, HPAI A(H5N1), and HPAI A(H5N6) isolates from humans in both or either models. They showed differential cellular tropism in human airway organoids; some infected all 4 major epithelial cell types: ciliated cells, club cells, goblet cells, and basal cells. Our results suggest zoonotic potential but low transmissibility of the HPAI A(H5N6/H5N8) avian isolates among humans. These viruses induced low levels of proinflammatory cytokines/chemokines, which are unlikely to contribute to the pathogenesis of severe disease.
Keywords	influenza ; human airway organoids ; risk assessment ; tropism ; innate host responses ; HPAI H5Nx ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Subject code	610
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Replication of SARS-CoV-2 Omicron BA.2 variant in ex vivo cultures of the human upper and lower respiratory tract

Kenrie P.Y. Hui / Ka-Chun Ng / John C.W. Ho / Hin-Wo Yeung / Rachel H.H. Ching / Haogao Gu / Joseph C.K. Chung / Velda L.Y. Chow / Ko-Yung Sit / Michael K.Y. Hsin / Timmy W.K. Au / Leo L.M. Poon / Malik Peiris / John M. Nicholls / Michael C.W. Chan

EBioMedicine, Vol 83, Iss , Pp 104232- (2022)

2022

Abstract: Summary: Background: The Omicron BA.2 sublineage has replaced BA.1 worldwide and has comparable levels of immune evasion to BA.1. These observations suggest that the increased transmissibility of BA.2 cannot be explained by the antibody evasion. Methods: ...

Abstract	Summary: Background: The Omicron BA.2 sublineage has replaced BA.1 worldwide and has comparable levels of immune evasion to BA.1. These observations suggest that the increased transmissibility of BA.2 cannot be explained by the antibody evasion. Methods: Here, we characterized the replication competence and respiratory tissue tropism of three Omicron variants (BA.1, BA.1.1, BA.2), and compared these with the wild-type virus and Delta variant, in human nasal, bronchial and lung tissues cultured ex vivo. Findings: BA.2 replicated more efficiently in nasal and bronchial tissues at 33°C than wild-type, Delta and BA.1. Both BA.2 and BA.1 had higher replication competence than wild-type and Delta viruses in bronchial tissues at 37°C. BA.1, BA.1.1 and BA.2 replicated at a lower level in lung parenchymal tissues compared to wild-type and Delta viruses. Interpretation: Higher replication competence of Omicron BA.2 in the human upper airway at 33°C than BA.1 may be one of the reasons to explain the current advantage of BA.2 over BA.1. A lower replication level of the tested Omicron variants in human lung tissues is in line with the clinical manifestations of decreased disease severity of patients infected with the Omicron strains compared with other ancestral strains. Funding: This work was supported by US National Institute of Allergy and Infectious Diseases and the Theme-Based Research Scheme under University Grants Committee of Hong Kong Special Administrative Region, China.
Keywords	SARS-CoV-2 ; Omicron BA.2 ; Nasal tissue ; Bronchial tissue ; Transmission ; Pathogenicity ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702

Alex W. H. Chin / Nathaniel K. C. Leong / John M. Nicholls / Leo L. M. Poon

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 12

Abstract: Abstract The 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range. Limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the ... ...

Abstract	Abstract The 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range. Limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the polymerase. In this study, we generated 31 viable viruses by random mutagenesis at this region, indicating that these positions can tolerate a wide range of amino acids. These mutants demonstrated varying polymerase activities and viral replication rates in mammalian and avian cells. Notably, some mutants displayed enhanced polymerase activity, yet their replication kinetics were comparable to the wild-type virus. Surface electrostatic charge predication on the PB2 structural model revealed that the viral polymerase activity in mammalian cells generally increases as this region becomes more positively charged. One of the mutants (701A/702E) showed much reduced pathogenicity in mice while others had a pathogenicity similar to the wild-type level. Distinct tissue tropisms of the PB2-701/702 mutants were observed in infected chicken embryos. Overall, this study demonstrates that the PB2-701/702 region has a high degree of sequence plasticity and sequence changes in this region can alter virus phenotypes in vitro and in vivo.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Eurasian Tree Sparrows, risk for H5N1 virus spread and human contamination through Buddhist ritual

Ramona Alikiiteaga Gutiérrez / San Sorn / John M Nicholls / Philippe Buchy

PLoS ONE, Vol 6, Iss 12, p e

an experimental approach.

2011 Volume 28609

Abstract: BACKGROUND: The Highly Pathogenic Avian Influenza H5N1 virus has dramatically spread throughout Southeast Asia since its first detection in 1997. Merit Release Birds, such as the Eurasian Tree Sparrow, are believed to increase one's positive karma when ... ...

Abstract	BACKGROUND: The Highly Pathogenic Avian Influenza H5N1 virus has dramatically spread throughout Southeast Asia since its first detection in 1997. Merit Release Birds, such as the Eurasian Tree Sparrow, are believed to increase one's positive karma when kissed and released during Buddhist rituals. Since these birds are often in close contact with both poultry and humans, we investigated their potential role in the spread of H5N1 virus. METHODOLOGY/PRINCIPAL FINDINGS: Seven series of experiments were conducted in order to investigate the possible interactions between inoculated and exposed birds, including sparrow/sparrow, sparrow/chicken, duck/sparrow. Daily and post-mortem samples collected were tested for H5N1 virus by real-time RT-PCR and egg inoculation. When directly inoculated, Eurasian Tree Sparrows were highly susceptible to the H5N1 virus, with a fatality rate approaching 100% within 5 days post-inoculation. Although transmission of fatal infection between sparrows did not occur, seroconversion of the exposed birds was observed. Up to 100% chickens exposed to inoculated sparrows died of H5N1 infection, depending on the caging conditions of the birds, while a fatality rate of 50% was observed on sparrows exposed to infected ducks. Large quantities of H5N1 virus were detected in the sparrows, particularly in their feathers, from which infectious particles were recovered. CONCLUSIONS/SIGNIFICANCE: Our study indicates that under experimental conditions, Eurasian Tree Sparrows are susceptible to H5N1 infection, either by direct inoculation or by contact with infected poultry. Their ability to transmit H5N1 infection to other birds is also demonstrated, suggesting that the sparrows may play a role in the dissemination of the virus. Finally, the presence of significant quantities of H5N1 virus on sparrows' feathers, including infectious particles, would suggest that Merit Release Birds represent a risk for human contamination in countries where avian influenza virus is circulating and where this religious ...
Keywords	Medicine ; R ; Science ; Q
Subject code	590
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Introduction of ORF3a-Q57H SARS-CoV-2 Variant Causing Fourth Epidemic Wave of COVID-19, Hong Kong, China

Daniel K.W. Chu / Kenrie P.Y. Hui / Haogao Gu / Ronald L.W. Ko / Pavithra Krishnan / Daisy Y.M. Ng / Gigi Y.Z. Liu / Carrie K.C. Wan / Man-Chun Cheung / Ka-Chun Ng / John M. Nicholls / Dominic N.C. Tsang / Malik Peiris / Michael C.W. Chan / Leo L.M. Poon

Emerging Infectious Diseases, Vol 27, Iss 5, Pp 1492-

2021 Volume 1495

Abstract: We describe an introduction of clade GH severe acute respiratory syndrome coronavirus 2 causing a fourth wave of coronavirus disease in Hong Kong. The virus has an ORF3a-Q57H mutation, causing truncation of ORF3b. This virus evades induction of cytokine, ...

Abstract	We describe an introduction of clade GH severe acute respiratory syndrome coronavirus 2 causing a fourth wave of coronavirus disease in Hong Kong. The virus has an ORF3a-Q57H mutation, causing truncation of ORF3b. This virus evades induction of cytokine, chemokine, and interferon-stimulated gene expression in primary human respiratory cells.
Keywords	respiratory infections ; severe acute respiratory syndrome coronavirus 2 ; SARS-CoV-2 ; SARS ; COVID-19 ; coronavirus disease ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Highly pathogenic influenza A(H5N1) virus survival in complex artificial aquatic biotopes.

Viseth Srey Horm / Ramona A Gutiérrez / John M Nicholls / Philippe Buchy

PLoS ONE, Vol 7, Iss 4, p e

2012 Volume 34160

Abstract: BACKGROUND: Very little is known regarding the persistence of Highly Pathogenic Avian Influenza (HPAI) H5N1 viruses in aquatic environments in tropical countries, although environmental materials have been suggested to play a role as reservoirs and ... ...

Abstract	BACKGROUND: Very little is known regarding the persistence of Highly Pathogenic Avian Influenza (HPAI) H5N1 viruses in aquatic environments in tropical countries, although environmental materials have been suggested to play a role as reservoirs and sources of transmission for H5N1 viruses. METHODOLOGY/PRINCIPAL FINDINGS: The survival of HPAI H5N1 viruses in experimental aquatic biotopes (water, mud, aquatic flora and fauna) relevant to field conditions in Cambodia was investigated. Artificial aquatic biotopes, including simple ones containing only mud and water, and complex biotopes involving the presence of aquatic flora and fauna, were set up. They were experimentally contaminated with H5N1 virus. The persistence of HPAI H5N1 virus (local avian and human isolates) was determined by virus isolation in embryonated chicken eggs and by real-time reverse-polymerase chain reaction. Persistence of infectious virus did not exceed 4 days, and was only identified in rain water. No infectious virus particles were detected in pond and lake water or mud even when high inoculum doses were used. However, viral RNA persisted up to 20 days in rain water and 7 days in pond or lake water. Viral RNA was also detected in mud samples, up to 14 days post-contamination in several cases. Infectious virus and viral RNA was detected in few cases in the aquatic fauna and flora, especially in bivalves and labyrinth fish, although these organisms seemed to be mostly passive carriers of the virus rather than host allowing virus replication. CONCLUSIONS/SIGNIFICANCE: Although several factors for the survival and persistence of HPAI viruses in the environment are still to be elucidated, and are particularly hard to control in laboratory conditions, our results, along with previous data, support the idea that environmental surveillance is of major relevance for avian influenza control programs.
Keywords	Medicine ; R ; Science ; Q
Subject code	333
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Identification of a wide spectrum of ciliary gene mutations in nonsyndromic biliary atresia patients implicates ciliary dysfunction as a novel disease mechanism

Wai-Yee Lam / Clara Sze-Man Tang / Man-Ting So / Haibing Yue / Jacob Shujui Hsu / Patrick Ho-Yu Chung / John M. Nicholls / Fanny Yeung / Chun-Wai Davy Lee / Diem Ngoc Ngo / Pham Anh Hoa Nguyen / Hannah M. Mitchison / Dagan Jenkins / Christopher O'Callaghan / Maria-Mercè Garcia-Barceló / So-Lun Lee / Pak-Chung Sham / Vincent Chi-Hang Lui / Paul Kwong-Hang Tam

EBioMedicine, Vol 71, Iss , Pp 103530- (2021)

2021

Abstract: Background: Biliary atresia (BA) is the most common obstructive cholangiopathy in neonates, often progressing to end-stage cirrhosis. BA pathogenesis is believed to be multifactorial, but the genetic contribution, especially for nonsyndromic BA (common ... ...

Abstract	Background: Biliary atresia (BA) is the most common obstructive cholangiopathy in neonates, often progressing to end-stage cirrhosis. BA pathogenesis is believed to be multifactorial, but the genetic contribution, especially for nonsyndromic BA (common form: > 85%) remains poorly defined. Methods: We conducted whole exome sequencing on 89 nonsyndromic BA trios to identify rare variants contributing to BA etiology. Functional evaluation using patients’ liver biopsies, human cell and zebrafish models were performed. Clinical impact on respiratory system was assessed with clinical evaluation, nasal nitric oxide (nNO), high speed video analysis and transmission electron microscopy. Findings: We detected rare, deleterious de novo or biallelic variants in liver-expressed ciliary genes in 31.5% (28/89) of the BA patients. Burden test revealed 2.6-fold (odds ratio (OR) [95% confidence intervals (CI)]= 2.58 [1.15–6.07], adjusted p = 0.034) over-representation of rare, deleterious mutations in liver-expressed ciliary gene set in patients compared to controls. Functional analyses further demonstrated absence of cilia in the BA livers with KIF3B and TTC17 mutations, and knockdown of PCNT, KIF3B and TTC17 in human control fibroblasts and cholangiocytes resulted in reduced number of cilia. Additionally, CRISPR/Cas9-engineered zebrafish knockouts of KIF3B, PCNT and TTC17 displayed reduced biliary flow. Abnormally low level of nNO was detected in 80% (8/10) of BA patients carrying deleterious ciliary mutations, implicating the intrinsic ciliary defects. Interpretation: Our findings support strong genetic susceptibility for nonsyndromic BA. Ciliary gene mutations leading to cholangiocyte cilia malformation and dysfunction could be a key biological mechanism in BA pathogenesis. Funding: The study is supported by General Research Fund, HMRF Commissioned Paediatric Research at HKCH and Li Ka Shing Faculty of Medicine Enhanced New Staff Start-up Fund.
Keywords	Biliary atresia ; Whole exome sequencing ; Rare variants ; Cilia dysfunction ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610 ; 616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Proinflammatory cytokine response and viral replication in mouse bone marrow derived macrophages infected with influenza H1N1 and H5N1 viruses.

Renee W Y Chan / Connie Y H Leung / John M Nicholls / J S Malik Peiris / Michael C W Chan

PLoS ONE, Vol 7, Iss 11, p e

2012 Volume 51057

Abstract: The pathogenesis of human influenza H5N1 virus infection remains poorly understood and controversial. Cytokine dysregulation in human infection has been hypothesized to contribute to disease severity. We developed in vitro cultures of mouse bone marrow ... ...

Abstract	The pathogenesis of human influenza H5N1 virus infection remains poorly understood and controversial. Cytokine dysregulation in human infection has been hypothesized to contribute to disease severity. We developed in vitro cultures of mouse bone marrow derived macrophages (BMDMΦ) from C57BL/6N mouse to compare influenza A (H5N1 and H1N1) virus replication and pro-inflammatory cytokine and chemokine responses. While both H1N1 and H5N1 viruses infected the mouse bone marrow derived macrophages, only the H1N1 virus had showed evidence of productive viral replication from the infected cells. In comparison with human seasonal influenza H1N1 (A/HK/54/98) and mouse adapted influenza H1N1 (A/WSN/33) viruses, the highly pathogenic influenza H5N1 virus (A/HK/483/97) was a more potent inducer of the chemokine, CXCL 10 (IP-10), while there was not a clear differential TNF-α protein expression pattern. Although human influenza viruses rarely cause infection in mice without prior adaption, the use of in vitro cell cultures of primary mouse cells is of interest, especially given the availability of gene-defective (knock-out) mice for specific genes.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED