EY1920 Year Book

63 62 Chui Ka Ho Tropism and pathogenesis of influenza A/H1N1 and A/H3N2 variants in human respiratory tract, an analysis in in vitro cells, ex vivo explants and organoid cultures Background Experimental models were developed to investigate the tropism and pathogenesis of influenza viruses. Here, the replication competence and cytokine induction profiles of influenza viruses in A549 cells (a human adenocarcinoma cell line resembling type II pneumocytes) and human airway organoids were compared to human lung and bronchus explants to study how well the in vitro experimental models mimic the human respiratory tract. Methods A549 cells, human airway organoids and human bronchus and lung explants were infected with the 2009 pandemic H1N1 virus (A/Hong Kong/415742/2009; abbreviated as HK/415742), an H1N1 variant virus (A/Netherlands/3315/2016; abbreviated as NL/3315), an H3N2 variant virus (A/Indiana/08/2011; abbreviated as Ind/08) and a low pathogenic H9N2 virus (A/Quail/Hong Kong/G1/1997; abbreviated as Quail/HK/G1. The replication competence and cytokine and chemokine induction profiles of the viruses in the aforementioned experimental models were studied. Results The 2 variant viruses had stronger replication competence than the other 2 viruses in A549 cells. Quail/HK/G1 was the strongest cytokine and chemokine inducer in A549 cells, while the 2 variant influenza A viruses produced inflammatory responses similar to that of HK/415742. In human airway organoids, all 4 influenza A viruses replicated with similar efficiency. Quail/HK/G1 was the strongest cytokine and chemokine inducer. NL/3315 induced significant upregulation of RANTES, IFN-β, IL-1β and MCP-1, while Ind/08 produced a weak inflammatory response. Upregulation of TRAIL was seen in all virus-infected A549 cells and human airway organoids, but the expression of TGF-β did not show substantial change in virus-infected samples compared to mock-infected samples. All viruses replicated with similar efficiency in human bronchus and lung explants, but to lower viral titres compared to their in vitro counterparts. Discussion The productive replication of the 2 variant influenza A viruses in the cell lines, airway organoids and respiratory tract explants showed the ability of the variant viruses to replicate in the human respiratory tract. NL/3315 produced stronger inflammatory responses in both A549 cells and human airway organoids than Ind/08, suggesting NL/3315 may be the stronger cytokine inducing agent. The data verified the use of cell lines and airway organoids as appropriate in vitro models of the respiratory tract, and hinted the potential of the 2 variant influenza viruses to cause disease in humans. However, investigating the cell types the influenza A viruses preferentially infect and the responses of virus-infected alveolar macrophages could have added more value to this study. Airway Organoids Cell Lines Human Explant Cultures MBBS Enrichment Year 2019/20 Chui Ka Ho Full Year < RA - T r op i sm an d p ath o gene s i s of in f luen z a A/ H 1 N 1 an d A/ H 3 N 2 v ariant s in hu m an re sp irat o r y tra c t , an anal ys i s in in v itr o c ell s, e x v i vo e xp lant s an d o rgan o i d c ulture s at Sc h oo l of Pu b li c Health , HK U, H o ng K o ng > Semester one: Study abroad at University of California, San Diego ⬆ crossed the border to volunteer in a student-run clinic for undeserved population in Tijuana " I couldn’t ask for a better exchange experience at UCSD. From all the lifelong friends I made to every spontaneous adventure I embarked on, I have learnt many different cultures, become a global citizen and grown a lot as a person. breathtaking views from Yosemite National Park, CA ⬆ � ⬅ the world-famous Geisel Library on campus that resembles a UFO moments before an emotional goodbye to my best friend, Pedro from Anaheim, CA ⬇ Semester two: Research Attachment at HKU I conducted a literature review on HCC guidelines in Hong Kong. I wish to further expand my breath and depth of this topic in clinical years. Not knowing what to expect beforehand, I now have a deeper insight into the importance of research which enables me to better prepare myself as a medical student. ⬆ Hong Kong Liver Cancer (HKLC) staging system MBBS Enrichment Year 2019/20 Chui Man Nok Arnold Sem 1 < IC - HKUWW Exchange Programme at University of California, San Diego, US >; Sem 2 < R A - Liver Cancer in Hong Kong; HCC guidelines in Hong Kong at D e p artment of Surgery, HKU, Hong Kong > Chui Man Nok Arnold