1,281 research outputs found
One world, one health
No full textThe past year has underscored the threat that emerging viruses pose to global health. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options for control of newly emerging infectious disease outbreaks in Asia, notably zoonotic influenza and severe acute respiratory syndrome (SARS). Nicole Neuman of Cell corresponded with Malik Peiris about his path to studying emerging infectious diseases and the challenges of this work. Excerpts of their exchange are included here. © 2021link_to_OA_fulltex
Susceptibility of human macrophages to influenza A infection
No full textThe seasonal Influenza A viruses are respiratory pathogens causing epidemics annually with mild illnesses, while sporadically, novel influenza viruses emerge and trigger pandemics associated with more widespread and sometimes severe disease. The biological basis for severity of influenza disease remains unclear though it is recognized that the interplay between the influenza viruses and the host immune responses both contribute to viral pathogenesis. As macrophages are key sentinels of the innate immune response and play a crucial role in being the “first responders” as well as contributing to shaping the subsequent (pathogen‐specific) adaptive immune response, the objective of this research was to bring insights on the outcomes of the interactions of influenza viruses with the macrophages.
The occurrence of Antibody‐Dependent Enhancement (ADE) of Influenza infection in macrophages was investigated. ADE occurs when non‐neutralized virus‐antibody complexes find alternative entry routes into host cells, mainly through the Fc‐receptor pathway and has been demonstrated predominantly in macrophages. Addition of human serum from some individuals to influenza A virus (either H5 pseudoparticles or pandemic (H1N1) virus) led to enhanced infection of murine macrophage‐like cells as illustrated by a two to five fold increase in detection of influenza M‐gene copies. Immunofluorescence microscopy indicated that serum‐mediated pandemic (H1N1) infection led to an increase in the number of infected cells than in controls. As the fold change in viral gene copies paralleled the fold increase of infected cells I concluded that ADE infection provide pandemic (H1N1) virus with increased opportunity to infect cells rather than simply increase the viral load per cell. In order to strengthen our results, and make them more physiologically relevant, experiments were then performed with human primary cells with clinical sera. However, ADE was not demonstrated in primary human macrophages, suggesting that ADE may be cell type or host specific.
The second research question investigated was whether the different state of human primary macrophage differentiation or activation in vitro determined the susceptibility to influenza infection. Recently, work by others has shown a diverse range of macrophage phenotypes that arise by differences in macrophage differentiation and activation. In addition to the classical activation pathway (caMΦ), new mechanisms of activation, designated as alternative
activation (aaMΦ), have been reported. Classically and alternatively activated macrophages display different phenotypes and properties, such as molecule expression patterns, cytokine secretion, and gene signatures. This study constitutes the first systematic comparison of Influenza A virus infection of these different subsets of human primary monocyte‐derived macrophages. When assessed for their permissiveness to different influenza A viruses, aaMΦΦshowed greater susceptibility to influenza A infection than caMΦ. This work also documents the receptor patterns and the gene expression profile of these macrophages in response to influenza virus infection in vitro. The results point to differences in susceptibility of the classically and alternatively activated human macrophages to pandemic H1N1 and other influenza A viruses and reveal intrinsic differences between these macrophage subtypes. Further investigations are needed to define the cellular and molecular determinants that define susceptibility of different macrophage subsets to influenza A infection.published_or_final_versionPublic HealthDoctoralDoctor of Philosoph
Innate immune responses and signaling pathways in influenza A (H5N1) infected human primary macrophages
No full textpublished_or_final_versionMicrobiologyDoctoralDoctor of Philosoph
Ecology, epidemiology and immunology of avian influenza virus
No full textpublished_or_final_versionMicrobiologyDoctoralDoctor of Philosoph
Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam
No full textBACKGROUND: Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses. METHODS AND FINDINGS: Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found. CONCLUSION: In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended
Influenza A virus replication and cytokine responses in murine macrophages in vitro
No full textpublished_or_final_versionabstractMicrobiologyMasterMaster of Philosoph
Response of human primary monocyte-derived macrophages to infection with highly pathogenic human influenza a virus subtype H5N1
No full textThe Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prizepublished_or_final_versionabstracttocMicrobiologyDoctoralDoctor of Philosoph
Ecology and evolution of swine influenza virus in Sri Lanka
No full textInfluenza A virus infections in pigs is a disease of concern to the swine industry and to the ecology and epidemiology of influenza viruses in humans. Pigs have been proposed as a “mixing vessel” for generation of pandemics via reassortment between avian and mammalian viruses. The H1N1pdm 2009 virus probably emerged from swine into humans though reassortment between the recent North American triple reassortant H1N2 swine viruses and Eurasian avian-like swine viruses.
Swine influenza viruses of H1N1, H1N2 and H3N2 subtypes have been regularly detected in pigs in most parts of the world. Nevertheless, ecological and virological data on swine influenza is not available in Sri Lanka, and indeed, little documented data is available in the South Asian continent. The swine population in Sri Lanka is about 80,000, and live pigs are not regularly imported to the country. Swine husbandry is largely confined to four neighboring administrative districts in the country.
Systematic virological and serological surveillance carried in swine abattoirs in Sri Lanka during 2009-2013 detected H1N1pdm 2009 like virus in local herds. Infection in pigs followed each of the H1N1pdm 2009 outbreaks in humans; October 2009 – January 2010, October 2010 – February 2011 and November 2012 – March 2013, respectively. Genetic, phylogenetic, and epidemiologic analysis of the human, and swine influenza viruses indicated spillover events of H1N1pdm 2009 from humans into pigs, with self-limited transmission and extinction within pig herds. The data also indicated that although H1N1pdm 2009 was able to spill over from humans to swine, it is not ideally adapted to establish sustained transmission among swine in the absence of further reassortment with other swine influenza virus lineages.
Theses finding might reflect characteristics of swine husbandry in Sri Lanka, which has a low density pig population and remains isolated from global swine influenza viruses because of the absence of regular cross-border and cross-continental movements of swine. In contrast to some other parts of the world, we failed to isolate established lineages of swine influenza viruses, viz. Classical, North American triple reassortant and European Avian lineages. Sero prevalence to these endemic swine viruses was largely absent in local swine herds.
In vitro replicative kinetic study indicated that H1N1pdm 2009 viruses isolated from swine have undergone some adaptation to swine led to decreased fitness for replication in human cells.published_or_final_versionPublic HealthDoctoralDoctor of Philosoph
Epidemiology and molecular genetics of verocytotoxigenic escherichia coli in Hong Kong
No full textpublished_or_final_versionMicrobiologyDoctoralDoctor of Philosoph
Human herpesvirus 6 (HHV-6) mRNA in peripheral blood leukocytes differentiates active infection from latency
No full textpublished_or_final_versionMicrobiologyMasterMaster of Philosoph
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