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  1. Article ; Online: Reply to: Population genetic considerations regarding the interpretation of within-patient SARS-CoV-2 polymorphism data.

    Nelson, Chase W / Poon, Leo L M / Gu, Haogao

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 3239

    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Polymorphism, Genetic ; Genetics, Population
    Language English
    Publishing date 2024-04-16
    Publishing country England
    Document type Letter
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46262-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses.

    Gu, Haogao / Chu, Daniel K W / Peiris, Malik / Poon, Leo L M

    Virus evolution

    2020  Volume 6, Issue 1, Page(s) veaa032

    Abstract: Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the ... ...

    Abstract Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus
    Keywords covid19
    Language English
    Publishing date 2020-05-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veaa032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Single-cycle influenza virus vaccine generates lung CD8

    Zheng, Ming Z M / Tan, Tiong Kit / Villalon-Letelier, Fernando / Lau, Hilda / Deng, Yi-Mo / Fritzlar, Svenja / Valkenburg, Sophie A / Gu, Haogao / Poon, Leo L M / Reading, Patrick C / Townsend, Alain R / Wakim, Linda M

    Science advances

    2023  Volume 9, Issue 36, Page(s) eadg3469

    Abstract: Influenza virus-specific tissue-resident memory (Trm) ... ...

    Abstract Influenza virus-specific tissue-resident memory (Trm) CD8
    MeSH term(s) Humans ; Influenza Vaccines ; CD8-Positive T-Lymphocytes ; Influenza, Human/prevention & control ; Immunization ; Levonorgestrel ; Nucleoproteins/genetics ; Lung
    Chemical Substances Influenza Vaccines ; Levonorgestrel (5W7SIA7YZW) ; Nucleoproteins
    Language English
    Publishing date 2023-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adg3469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Dinucleotide evolutionary dynamics in influenza A virus.

    Gu, Haogao / Fan, Rebecca L Y / Wang, Di / Poon, Leo L M

    Virus evolution

    2019  Volume 5, Issue 2, Page(s) vez038

    Abstract: Significant biases of dinucleotide composition in many RNA viruses including influenza A virus have been reported in recent years. Previous studies have showed that a codon-usage-altered influenza mutant with elevated CpG usage is attenuated in ... ...

    Abstract Significant biases of dinucleotide composition in many RNA viruses including influenza A virus have been reported in recent years. Previous studies have showed that a codon-usage-altered influenza mutant with elevated CpG usage is attenuated in mammalian
    Language English
    Publishing date 2019-09-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/vez038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children.

    Jia, Janice Z / Cohen, Carolyn A / Gu, Haogao / McLean, Milla R / Varadarajan, Raghavan / Bhandari, Nisha / Peiris, Malik / Leung, Gabriel M / Poon, Leo L M / Tsang, Tim / Chung, Amy W / Cowling, Benjamin J / Leung, Nancy H L / Valkenburg, Sophie A

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 3210

    Abstract: Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent ... ...

    Abstract Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered 'elite influenza controllers'.
    MeSH term(s) Child ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Prospective Studies ; Antibodies, Viral ; Antibodies, Neutralizing ; Immunoglobulin G ; Influenza Vaccines
    Chemical Substances Antibodies, Viral ; Antibodies, Neutralizing ; Immunoglobulin G ; Influenza Vaccines
    Language English
    Publishing date 2024-04-13
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-47590-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Multivariate Analyses of Codon Usage of SARS-CoV-2 and other betacoronaviruses

    Gu, Haogao / Chu, Daniel / Peiris, Malik / Poon, Leo L.M.

    bioRxiv

    Keywords covid19
    Language English
    Publishing date 2020-02-25
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.02.15.950568
    Database COVID19

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  7. Article ; Online: Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.

    Bull, Maireid B / Gu, Haogao / Ma, Fionn N L / Perera, Liyanage P / Poon, Leo L M / Valkenburg, Sophie A

    Science advances

    2022  Volume 8, Issue 14, Page(s) eabl5209

    Abstract: To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell-based vaccine, an H5N1-based viral ... ...

    Abstract To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell-based vaccine, an H5N1-based viral vectored vaccinia vaccine Wyeth/IL-15/5Flu, versus the current standard-of-care, seasonal inactivated influenza vaccine (IIV) and unvaccinated conditions. Wyeth/IL-15/5Flu vaccination was coincident with increased mutation incidence and frequency across the influenza genome; however, mutations were not enriched within T cell epitope regions, but high allele frequency mutations within conserved hemagglutinin stem regions and PB2 mammalian adaptive mutations arose. Depletion of CD4
    MeSH term(s) Animals ; Genome, Viral ; Humans ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza Vaccines ; Influenza, Human/prevention & control ; Interleukin-15/genetics ; Mice ; Mutation ; Orthomyxoviridae Infections ; Prevalence ; Vaccination
    Chemical Substances Influenza Vaccines ; Interleukin-15
    Language English
    Publishing date 2022-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abl5209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice.

    Chu, Julie Ts / Gu, Haogao / Sun, Wanying / Fan, Rebecca Ly / Nicholls, John M / Valkenburg, Sophie A / Poon, Leo Lm

    Virus research

    2022  Volume 323, Page(s) 198991

    Abstract: Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing ...

    Abstract Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that a suboptimial usage of population-wide universal influenza vaccine may drive formation of escape variants attributed to polygenic changes.
    Language English
    Publishing date 2022-10-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2022.198991
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Wastewater genomic sequencing for SARS-CoV-2 variants surveillance in wastewater-based epidemiology applications

    Xu, Xiaoqing / Deng, Yu / Ding, Jiahui / Zheng, Xiawan / Wang, Chunxiao / Wang, Dou / Liu, Lei / Gu, Haogao / Peiris, Malik / Poon, Leo L.M / Zhang, Tong

    Water Research. 2023 Aug. 03, p.120444-

    2023  , Page(s) 120444–

    Abstract: Wastewater-based epidemiology (WBE) has been widely used as a complementary approach to SARS-CoV-2 clinical surveillance. Wastewater genomic sequencing could provide valuable information on the genomic diversity of SARS-CoV-2 in the surveyed population. ... ...

    Abstract Wastewater-based epidemiology (WBE) has been widely used as a complementary approach to SARS-CoV-2 clinical surveillance. Wastewater genomic sequencing could provide valuable information on the genomic diversity of SARS-CoV-2 in the surveyed population. However, reliable detection and quantification of variants or mutations remain challenging. In this study, we used mock wastewater samples created by spiking SARS-CoV-2 variant standard RNA into wastewater RNA to evaluate the impacts of sequencing throughput on various aspects such as genome coverage, mutation detection, and SARS-CoV-2 variant deconvolution. We found that wastewater datasets with sequencing throughput greater than 0.5 Gb yielded reliable results in genomic analysis. In addition, using in silico mock datasets, we evaluated the performance of the adopted pipeline for variant deconvolution. By sequencing 86 wastewater samples covering more than 6 million people over a period of 7 months, we presented two use cases of wastewater genomic sequencing for surveying COVID-19 in Hong Kong in WBE applications, including the replacement of Delta variants by Omicron variants, and the prevalence and development trends of three Omicron sublineages. Importantly, the wastewater genomic sequencing data were able to reveal the variant trends 16 days before the clinical data did. By investigating mutations of the spike (S) gene of the SARS-CoV-2 virus, we also showed the potential of wastewater genomic sequencing in identifying novel mutations and unique alleles. Overall, our study demonstrated the crucial role of wastewater genomic surveillance in providing valuable insights into the emergence and monitoring of new SARS-CoV-2 variants and laid a solid foundation for the development of genomic analysis methodologies for WBE of other novel emerging viruses in the future.
    Keywords COVID-19 infection ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; computer simulation ; data collection ; epidemiology ; genes ; genetic variation ; genomics ; monitoring ; mutation ; people ; research ; viruses ; wastewater ; water ; China ; Wastewater-based epidemiology ; Wastewater genome sequencing ; SARS-CoV-2 ; Variant ; Surveillance
    Language English
    Dates of publication 2023-0803
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 202613-2
    ISSN 1879-2448 ; 0043-1354
    ISSN (online) 1879-2448
    ISSN 0043-1354
    DOI 10.1016/j.watres.2023.120444
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals.

    Gu, Haogao / Quadeer, Ahmed Abdul / Krishnan, Pavithra / Ng, Daisy Y M / Chang, Lydia D J / Liu, Gigi Y Z / Cheng, Samuel M S / Lam, Tommy T Y / Peiris, Malik / McKay, Matthew R / Poon, Leo L M

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 1793

    Abstract: Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples with ...

    Abstract Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples with different viral lineages to describe the patterns of within-host diversity under different conditions, including vaccine-breakthrough infections. In unvaccinated individuals, variant of Concern (VOC) Alpha, Delta, and Omicron respiratory samples were found to have higher within-host diversity and were under neutral to purifying selection at the full genome level compared to non-VOC SARS-CoV-2. Breakthrough infections in 2-dose or 3-dose Comirnaty and CoronaVac vaccinated individuals did not increase levels of non-synonymous mutations and did not change the direction of selection pressure. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 sequence diversification. Our findings suggest that vaccination does not increase exploration of SARS-CoV-2 protein sequence space and may not facilitate emergence of viral variants.
    MeSH term(s) Humans ; COVID-19/epidemiology ; COVID-19/prevention & control ; SARS-CoV-2/genetics ; Antibodies, Viral ; Breakthrough Infections ; COVID-19 Vaccines ; Mutation
    Chemical Substances sinovac COVID-19 vaccine ; Antibodies, Viral ; COVID-19 Vaccines
    Language English
    Publishing date 2023-03-31
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-37468-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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