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  1. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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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  3. 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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  4. Article ; Online: Generation of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines.

    Wang, Pui / Zheng, Min / Lau, Siu-Ying / Chen, Pin / Mok, Bobo Wing-Yee / Liu, Siwen / Liu, Honglian / Huang, Xiaofeng / Cremin, Conor J / Song, Wenjun / Chen, Yixin / Wong, Yik-Chun / Huang, Haode / To, Kelvin Kai-Wong / Chen, Zhiwei / Xia, Ningshao / Yuen, Kwok-Yung / Chen, Honglin

    mBio

    2019  Volume 10, Issue 5

    Abstract: Nonstructural protein 1 (NS1) of influenza virus is a key virulence element with multifunctional roles in virus replication and a potent antagonist of host immune response. Deletion of NS1 (DelNS1) would create a safer and more extensively immunogenic ... ...

    Abstract Nonstructural protein 1 (NS1) of influenza virus is a key virulence element with multifunctional roles in virus replication and a potent antagonist of host immune response. Deletion of NS1 (DelNS1) would create a safer and more extensively immunogenic live attenuated influenza virus (LAIV) vaccine. However, DelNS1 viruses are very difficult to grow in regular vaccine-producing systems, which has hampered the application of DelNS1 LAIV vaccines in humans. We have developed two master backbones of deleted-NS1 (DelNS1) viral genomes from influenza A or B viruses which contain novel adaptive mutations to support DelNS1-LAIV replication. These DelNS1-LAIVs are highly attenuated in human cells
    MeSH term(s) Animals ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Cross Protection ; Female ; Gene Deletion ; Genome, Viral ; Humans ; Immunity, Humoral ; Immunogenicity, Vaccine ; Influenza A virus/genetics ; Influenza A virus/growth & development ; Influenza A virus/immunology ; Influenza B virus/genetics ; Influenza B virus/growth & development ; Influenza B virus/immunology ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Influenza, Human/prevention & control ; Mice ; Mice, Inbred BALB C ; Mutation ; Orthomyxoviridae/genetics ; Orthomyxoviridae/growth & development ; Orthomyxoviridae/immunology ; Orthomyxoviridae Infections/immunology ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Viral Nonstructural Proteins/genetics ; Virus Replication
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Influenza Vaccines ; Vaccines, Attenuated ; Viral Nonstructural Proteins
    Language English
    Publishing date 2019-09-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.02180-19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

    Mok, Bobo Wing Yee / Cremin, Conor J / Lau, Siu-Ying / Deng, Shaofen / Chen, Pin / Zhang, Anna Jinxia / Lee, Andrew Chak-Yiu / Liu, Honglian / Liu, Siwen / Ng, Timothy Ting-Leung / Lao, Hiu-Yin / Lee, Eddie Lam-Kwong / Leung, Kenneth Siu-Sing / Wang, Pui / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Chan, Kwok-Hung / Yuen, Kwok-Yung / Siu, Gilman Kit-Hang /
    Chen, Honglin

    bioRxiv

    Abstract: SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster ... ...

    Abstract SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.
    Keywords covid19
    Language English
    Publishing date 2020-08-28
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.08.28.271635
    Database COVID19

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  6. Article ; Online: SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters

    Mok, Bobo Wing-Yee / Cremin, Conor J. / Lau, Siu-Ying / Deng, Shaofeng / Chen, Pin / Zhang, Anna Jinxia / Lee, Andrew Chak-Yiu / Liu, Honglian / Liu, Siwen / Ng, Timothy Ting-Leung / Lao, Hiu-Yin / Lee, Eddie Lam-Kwong / Leung, Kenneth Siu-Sing / Wang, Pui / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Chan, Kwok-Hung / Yuen, Kwok-Yung / Siu, Gilman Kit-Hang /
    Chen, Honglin

    bioRxiv

    Abstract: SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster ... ...

    Abstract SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.
    Keywords covid19
    Publisher BioRxiv; WHO
    Document type Article ; Online
    DOI 10.1101/2020.08.28.271635
    Database COVID19

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