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Article ; Online: Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges.

Lee, Andrew Chak-Yiu / Zhang, Anna Jinxia / Li, Can / Chen, Yanxia / Liu, Feifei / Zhao, Yan / Chu, Hin / Fong, Carol Ho-Yan / Wang, Pui / Lau, Siu-Ying / To, Kelvin Kai-Wang / Chen, Honglin / Yuen, Kwok-Yung

NPJ vaccines

2021 Volume 6, Issue 1, Page(s) 95

Abstract: We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) ... ...

Abstract	We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) vaccination induces protective immunity. Our results showed that DelNS1-LAIV intradermal vaccination conferred effective and long-lasting protection against lethal virus challenge in mice. A single intradermal injection of DelNS1-LAIV conferred 100% survival with no weight loss in mice after A(H1N1)09 influenza virus (H1N1/415742Md) challenge. DelNS1-LAIV injection resulted in a significant reduction of lung viral load and reduced airway epithelial cell death and lung inflammatory cytokine responses at day 2 and 4 post challenge. Full protections of mice lasted for 6 months after immunization. In vitro infection of DelNS1-LAIV in monocyte-derived dendritic cells (MoDCs) demonstrated activation of antigen-presenting cells at 33 °C, together with the results of abortive replication of DelNS1-LAIV in skin tissue and strong upregulation of inflammatory cytokines/chemokines expression, our results suggested the strong immunogenicity of this vaccine. Further, we demonstrate that the underlying protection mechanism induced by intradermal DelNS1-LAIV is mainly attributed to antibody responses. Together, this study opens up an alternative route for the administration of LAIV, which may benefit individuals not suitable for intranasal LAIV immunization.
Language	English
Publishing date	2021-08-04
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-021-00359-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Low dose inocula of SARS-CoV-2 Alpha variant transmits more efficiently than earlier variants in hamsters.

Mok, Bobo Wing-Yee / Liu, Honglian / Deng, Shaofeng / Liu, Jiayan / Zhang, Anna Jinxia / Lau, Siu-Ying / Liu, Siwen / Tam, Rachel Chun-Yee / Cremin, Conor J / Ng, Timothy Ting-Leung / Leung, Jake Siu-Lun / Lee, Lam-Kwong / Wang, Pui / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Chan, Kwok-Hung / Yuen, Kwok-Yung / Siu, Gilman Kit-Hang / Chen, Honglin

Communications biology

2021 Volume 4, Issue 1, Page(s) 1102

Abstract: Emerging variants of SARS-CoV-2 have been shown to rapidly replace original circulating strains in humans soon after they emerged. There is a lack of experimental evidence to explain how these natural occurring variants spread more efficiently than ... ...

Abstract	Emerging variants of SARS-CoV-2 have been shown to rapidly replace original circulating strains in humans soon after they emerged. There is a lack of experimental evidence to explain how these natural occurring variants spread more efficiently than existing strains of SARS-CoV-2 in transmission. We found that the Alpha variant (B.1.1.7) increased competitive fitness over earlier parental D614G lineages in in-vitro and in-vivo systems. Using hamster transmission model, we further demonstrated that the Alpha variant is able to replicate and shed more efficiently in the nasal cavity of hamsters than other variants with low dose and short duration of exposure. The capability to initiate effective infection with low inocula may be one of the key factors leading to the rapid transmission of emerging variants of SARS-CoV-2.
MeSH term(s)	Animals ; COVID-19/genetics ; COVID-19/pathology ; COVID-19/transmission ; Cell Line/virology ; Cricetinae ; Disease Models, Animal ; Humans ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Virus Replication/genetics
Language	English
Publishing date	2021-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-02640-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Initial Prostate Health Index (phi) and phi density predicts future risk of clinically significant prostate cancer in men with initial negative prostate biopsy: a 6-year follow-up study.

Liu, Alex Qinyang / Remmers, Sebastiaan / Lau, Sui-Yan / Yip, Siu-Ying / Leung, Chi-Ho / Mak, Christy Wing-Hin / Yee, Chi-Hang / Teoh, Jeremy Yuen-Chun / Hou, See-Ming / Roobol, Monique / Ng, Chi-Fai / Chiu, Peter Ka-Fung

Prostate cancer and prostatic diseases

2021 Volume 25, Issue 4, Page(s) 684–689

Abstract: Background: Men with elevated prostate-specific antigen (PSA) and initial negative prostate biopsy may have risk of prostate cancer (PCa) in the future. The role of Prostate Health Index (phi) in determining future PCa risk has not been studied before. ... ...

Abstract	Background: Men with elevated prostate-specific antigen (PSA) and initial negative prostate biopsy may have risk of prostate cancer (PCa) in the future. The role of Prostate Health Index (phi) in determining future PCa risk has not been studied before. This study aims to investigate the role of initial phi and phi density in predicting future PCa risk in men with initial negative biopsy. Methods: Five hundred sixty nine men with PSA 4-10 ng/mL were recruited between 2008 and 2015 for prostate biopsy with prior phi. Electronic clinical record of men with initial negative biopsy was reviewed. Patients and follow-up doctors were blinded to phi. Kaplan-Meier curves were used to analyze the PCa-free survival in different baseline phi and phi density groups. Results: Four hundred sixty-one men with complete follow-up data were included. Median follow-up is 77 months. PCa and HGPCa was diagnosed in 8.2% (38/461) and 4.8% (22/461) of cohort respectively. A higher baseline phi value was associated with PCa (p = 0.003) and HGPCa (p < 0.001). HGPCa was diagnosed in 0.6% (1/163) of phi < 25, 4.6% (9/195) of phi 25-34.9, and 11.7% (12/103) of phi ≥ 35 (p < 0.001). HGPCa was diagnosed in 0% (0/109) and 21.0% (13/62) with phi density of <0.4 and ≥1.2, respectively, (p < 0.001). Kaplan-Meier curves showed phi and phi density predicted PCa and HGPCa diagnoses (log-rank test, all p ≤ 0.002). Conclusions: Initial phi or phi density predicted 6-year risk of PCa in men with initial negative prostate biopsy. Men with higher phi (≥35) or phi density (≥1.2) need closer follow-up and repeated investigation, while men with lower phi (<25) or phi density (<0.4) could have less frequent follow-up.
MeSH term(s)	Male ; Humans ; Prostate/pathology ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/pathology ; Prostate-Specific Antigen ; Follow-Up Studies ; Biopsy
Chemical Substances	Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2021-08-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1419277-9
ISSN	1476-5608 ; 1365-7852
ISSN (online)	1476-5608
ISSN	1365-7852
DOI	10.1038/s41391-021-00444-y
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Article ; Online: Multiple Roads to Success: A Latent Class Analysis on Successful Ageing Among Hong Kong Near-Centenarians and Centenarians (NCC).

Shum, Eric Ngai-Yin / Lau, Bobo Hi-Po / Cheung, Karen Siu-Lan / Chan, Cecilia Lai-Wan / Siu, Joey Chung-Yue / Luk, James Ka-Hay / Kwan, Joseph Shiu-Kwong / Chan, Grace Man-Yee / Pat, Lian Ying-Chun / Martin, Peter

International journal of aging & human development

2023 , Page(s) 914150231208681

Abstract: Notwithstanding the oldest-old cohort being the fastest-growing population in most ageing societies, characterizing successful ageing in adults of advanced age, such as nonagenarians and centenarians, remains challenging. This study investigated the ... ...

Abstract	Notwithstanding the oldest-old cohort being the fastest-growing population in most ageing societies, characterizing successful ageing in adults of advanced age, such as nonagenarians and centenarians, remains challenging. This study investigated the successful ageing subphenotypes using the data from Hong Kong Centenarian Study 2. Between April 2021 and September 2022, 146 family caregivers of community-dwelling older adults aged 95 or above were interviewed by phone. Latent class analysis identified three classes-
Language	English
Publishing date	2023-10-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	187072-5
ISSN	1541-3535 ; 0091-4150
ISSN (online)	1541-3535
ISSN	0091-4150
DOI	10.1177/00914150231208681
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Article ; Online: Low dose inocula of SARS-CoV-2 B.1.1.7 variant initiate more robust infections in the upper respiratory tract of hamsters than earlier D614G variants

Mok, Bobo Wing-Yee / Liu, Honglian / Lau, Siu-Ying / Deng, Shaofeng Deng / Liu, Siwen / Tam, Rachel Chun-Yee / Ng, Timothy Ting-Leung / Leung, Jake Siu-Lun / Wang, Pui / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Chan, Kwok-Hung / Yuen, Kwok-Yung / Siu, Gilman Kit-Hang / Chen, Honglin

bioRxiv

Abstract: There is a lack of experimental evidence to explain how the B.1.1.7 variant spreads more quickly than pre-existing variants in humans. We found that B.1.1.7 displays increased competitive fitness over earlier D614G lineages in an in-vitro system. ... ...

Abstract	There is a lack of experimental evidence to explain how the B.1.1.7 variant spreads more quickly than pre-existing variants in humans. We found that B.1.1.7 displays increased competitive fitness over earlier D614G lineages in an in-vitro system. Furthermore, we demonstrated that B.1.1.7 variant is able to replicate and shed more efficiently in the nasal cavity than other variants with lower dose and shorter duration of exposure.
Keywords	covid19
Language	English
Publishing date	2021-04-19
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.04.19.440414
Database	COVID19

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Article ; Online: Mammalian cells use the autophagy process to restrict avian influenza virus replication.

Liu, Siwen / Mok, Bobo Wing-Yee / Deng, Shaofeng / Liu, Honglian / Wang, Pui / Song, Wenjun / Chen, Pin / Huang, Xiaofeng / Zheng, Min / Lau, Siu-Ying / Cremin, Conor J / Tam, Chun-Yee / Li, Baiying / Jiang, Liwen / Chen, Yixin / Yuen, Kwok-Yung / Chen, Honglin

Cell reports

2021 Volume 35, Issue 10, Page(s) 109213

Abstract: Host adaptive mutations in the influenza A virus (IAV) PB2 protein are critical for human infection, but their molecular action is not well understood. We observe that when IAV containing avian PB2 infects mammalian cells, viral ribonucleoprotein (vRNP) ... ...

Abstract	Host adaptive mutations in the influenza A virus (IAV) PB2 protein are critical for human infection, but their molecular action is not well understood. We observe that when IAV containing avian PB2 infects mammalian cells, viral ribonucleoprotein (vRNP) aggregates that localize to the microtubule-organizing center (MTOC) are formed. These vRNP aggregates resemble LC3B-associated autophagosome structures, with aggresome-like properties, in that they cause the re-distribution of vimentin. However, electron microscopy reveals that these aggregates represent an accumulation of autophagic vacuoles. Compared to mammalian-PB2 virus, avian-PB2 virus induces higher autophagic flux in infected cells, indicating an increased rate of autophagosomes containing avian vRNPs fusing with lysosomes. We found that p62 is essential for the formation of vRNP aggregates and that the Raptor-interacting region of p62 is required for interaction with vRNPs through the PB2 polymerase subunit. Selective autophagic sequestration during late-stage virus replication is thus an additional strategy for host restriction of avian-PB2 IAV.
MeSH term(s)	Animals ; Autophagy/genetics ; Birds ; Cell Line ; Influenza A virus/pathogenicity ; Influenza in Birds/virology ; Virus Replication/genetics
Language	English
Publishing date	2021-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109213
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Article ; Online: Low dose inocula of SARS-CoV-2 Alpha variant transmits more efficiently than earlier variants in hamsters

Bobo Wing-Yee Mok / Honglian Liu / Shaofeng Deng / Jiayan Liu / Anna Jinxia Zhang / Siu-Ying Lau / Siwen Liu / Rachel Chun-Yee Tam / Conor J. Cremin / Timothy Ting-Leung Ng / Jake Siu-Lun Leung / Lam-Kwong Lee / Pui Wang / Kelvin Kai-Wang To / Jasper Fuk-Woo Chan / Kwok-Hung Chan / Kwok-Yung Yuen / Gilman Kit-Hang Siu / Honglin Chen

Communications Biology, Vol 4, Iss 1, Pp 1-

2021 Volume 8

Abstract: Bobo Wing-Yee Mok et al. observe that the Alpha (B.1.1.7) variant of SARS-CoV-2 exhibits increased competitive fitness over earlier lineages at lower doses in a hamster model of viral transmission. Their results suggest that the Alpha variant’s ability ... ...

Abstract	Bobo Wing-Yee Mok et al. observe that the Alpha (B.1.1.7) variant of SARS-CoV-2 exhibits increased competitive fitness over earlier lineages at lower doses in a hamster model of viral transmission. Their results suggest that the Alpha variant’s ability to initiate effective infection with a low dose may underlie its ability to rapidly transmit throughout a population.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

Pui Wang / Siu-Ying Lau / Shaofeng Deng / Pin Chen / Bobo Wing-Yee Mok / Anna Jinxia Zhang / Andrew Chak-Yiu Lee / Kwok-Hung Chan / Rachel Chun-Yee Tam / Haoran Xu / Runhong Zhou / Wenjun Song / Li Liu / Kelvin Kai-Wang To / Jasper Fuk-Woo Chan / Zhiwei Chen / Kwok-Yung Yuen / Honglin Chen

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 10

Abstract: The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, ...

Abstract	The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, generation of potent adaptive immunity but reduced immunopathology in a hamster model of infection.
Keywords	Science ; Q
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SRPK2 Mediates HBV Core Protein Phosphorylation and Capsid Assembly via Docking Interaction.

Yip, Ryan Pak Hong / Kwok, Doris Ching Ying / Lai, Louis Tung Faat / Ho, Siu-Ming / Wong, Ivan Chun Kit / Chan, Chi-Ping / Lau, Wilson Chun Yu / Ngo, Jacky Chi Ki

PLoS pathogens

2024 Volume 20, Issue 2, Page(s) e1011978

Abstract: Members of the serine-arginine protein kinase (SRPK) family, SRPK1 and SRPK2, phosphorylate the hepatitis B core protein (Cp) and are crucial for pregenomic RNA encapsidation during viral nucleocapsid assembly. Among them, SRPK2 exhibits higher kinase ... ...

Abstract	Members of the serine-arginine protein kinase (SRPK) family, SRPK1 and SRPK2, phosphorylate the hepatitis B core protein (Cp) and are crucial for pregenomic RNA encapsidation during viral nucleocapsid assembly. Among them, SRPK2 exhibits higher kinase activity toward Cp. In this study, we identified Cp sites that are phosphorylated by SRPK2 and demonstrated that the kinase utilizes an SRPK-specific docking groove to interact with and regulate the phosphorylation of the C-terminal arginine rich domain of Cp. We determined that direct interaction between the docking groove of SRPK2 and unphosphorylated Cp inhibited premature viral capsid assembly in vitro, whereas the phosphorylation of the viral protein reactivated the process. Pull-down assays together with the new cryo-electron microscopy structure of the HBV capsid in complex with SRPK2 revealed that the kinases decorate the surface of the viral capsid by interacting with the C-terminal domain of Cp, underscoring the importance of the docking interaction in regulating capsid assembly and pregenome packaging. Moreover, SRPK2-knockout in HepG2 cells suppressed Cp phosphorylation, indicating that SRPK2 is an important cellular kinase for HBV life cycle.
MeSH term(s)	Phosphorylation ; Capsid/metabolism ; Hepatitis B virus/metabolism ; Cryoelectron Microscopy ; Protein Serine-Threonine Kinases/metabolism ; Capsid Proteins/metabolism ; Virus Assembly/physiology ; Arginine/metabolism
Chemical Substances	Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Capsid Proteins ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011978
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans.

Wang, Pui / Song, Wenjun / Mok, Bobo Wing-Yee / Zheng, Min / Lau, Siu-Ying / Liu, Siwen / Chen, Pin / Huang, Xiaofeng / Liu, Honglian / Cremin, Conor J / Chen, Honglin

Viruses

2019 Volume 11, Issue 3

Abstract: Significantly higher numbers of human infections with H5N1 virus have occurred in Indonesia and Egypt, compared with other affected areas, and it is speculated that there are specific viral factors for human infection with avian H5N1 viruses in these ... ...

Abstract	Significantly higher numbers of human infections with H5N1 virus have occurred in Indonesia and Egypt, compared with other affected areas, and it is speculated that there are specific viral factors for human infection with avian H5N1 viruses in these locations. We previously showed PB2-K526R is present in 80% of Indonesian H5N1 human isolates, which lack the more common PB2-E627K substitution. Testing the hypothesis that this mutation may prime avian H5N1 virus for human infection, we showed that: (1) K526R is rarely found in avian influenza viruses but was identified in H5N1 viruses 2⁻3 years after the virus emerged in Indonesia, coincident with the emergence of H5N1 human infections in Indonesia; (2) K526R is required for efficient replication of Indonesia H5N1 virus in mammalian cells in vitro and in vivo and reverse substitution to 526K in human isolates abolishes this ability; (3) Indonesian H5N1 virus, which contains K526R-PB2, is stable and does not further acquire E627K following replication in infected mice; and (4) virus containing K526R-PB2 shows no fitness deficit in avian species. These findings illustrate an important mechanism in which a host adaptive mutation that predisposes avian H5N1 virus towards infecting humans has arisen with the virus becoming prevalent in avian species prior to human infections occurring. A similar mechanism is observed in the Qinghai-lineage H5N1 viruses that have caused many human cases in Egypt; here, E627K predisposes towards human infections. Surveillance should focus on the detection of adaptation markers in avian strains that prime for human infection.
MeSH term(s)	Adaptation, Physiological ; Amino Acid Substitution ; Animals ; Birds ; Egypt ; Host-Pathogen Interactions/genetics ; Humans ; Indonesia ; Influenza A Virus, H5N1 Subtype/enzymology ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza in Birds/transmission ; Influenza in Birds/virology ; Influenza, Human/virology ; Mice ; Mice, Inbred BALB C ; Mutation, Missense ; Viral Proteins/genetics ; Virus Replication
Chemical Substances	PB2 protein, influenza virus ; Viral Proteins
Language	English
Publishing date	2019-03-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v11030292
Database	MEDical Literature Analysis and Retrieval System OnLINE

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