Tropism of influenza B viruses in human respiratory tract explants and airway organoids

Abstract

Despite causing regular seasonal epidemics with substantial morbidity, mortality and socioeconomic burden, there is still a lack of research into influenza B viruses (IBVs). In this study, we provide for the first time a systematic investigation on the tropism, replication kinetics and pathogenesis of IBVs in the human respiratory tract.Physiologically relevant ex vivo explant cultures of human bronchus and lung, human airway organoids, and in vitro cultures of differentiated primary human bronchial epithelial cells and type-I-like alveolar epithelial cells were used to study the cellular and tissue tropism, replication competence and induced innate immune response of 16 IBV strains isolated from 1940 to 2012 in comparison with human seasonal influenza A viruses (IAVs), H1N1 and H3N2. IBVs from the diverged Yamagata- and Victoria-like lineages and the earlier undiverged period were included.The majority of IBVs replicated productively in human bronchus and lung with similar competence to seasonal IAVs. IBVs infected a variety of cell types, including ciliated cells, club cells, goblet cells and basal cells, in human airway organoids. Like seasonal IAVs, IBVs are low inducers of pro-inflammatory cytokines and chemokines. Most results suggested a higher preference for the conducting airway than the lower lung and strain-specific rather than lineage-specific pathogenicity of IBVs.Our results highlighted the non-negligible virulence of IBVs which require more attention and further investigation to alleviate the disease burden, especially when treatment options are limited.

Identification of H3N2 NA and PB1-F2 genetic variants and their association with disease symptoms during the 2014-15 influenza season

“…Numerous studies used primary cells to show differences in replication of engineered and isolated influenza viruses (Bui et al, 2019;Danzy et al, 2014;Elderfield et al, 2014;Fischer et al, 2015;Gerlach et al, 2017;Monteagudo et al, 2019;Wohlgemuth et al, 2017). Here, we report that hNECs were more permissive for growth of virus isolates than MDCK cell cultures.…”

When “B” becomes “A”: the emerging threat of influenza B virus

“…Similarly, influenza B effectively infected and replicated in human lung transplant, showing its ability to cause severe lower respiratory tract infections which are often associated with the lethal disease. Interestingly, one striking difference that was observed in this study was the dependency of viral replication on mucin, which selectively inhibited influenza B but not influenza A strains [8]. Cell surface mucin, specifically MUC-1, is upregulated in lung infections.…”

“…These data strongly refute the claims that influenza B is the milder version of the flu. In this issue of the European Respiratory Journal, the study by BUI et al [8] sheds light on influenza B interactions within the human respiratory tract and lung to demonstrate its pathogenicity and its potential to spread and cause severe lung infections.…”

“…Host response to the influenza B virus is largely similar to the influenza A virus and recently circulating strains of influenza B have shown comparable pathogenicity to influenza A in mouse models [16]. The study by BUI et al [8] sheds important light on the tropism, replication ability and host immune response by a wide range of influenza B strains, including the strains obtained before the separation of influenza B into the two currently known lineages (Victoria-like and Yamagata-like strain). The authors used primary human bronchus, lung tissue and human airway organoids along with bronchial and alveolar epithelial cells to study these parameters.…”

Experimental Infection of Adapted Influenza B Virus in Mice Model

“…In Europe influenza B accounted for 63% of all influenza cases in the 2017-2018 epidemic season [8]. A number of studies using ex-vivo (explant) cultures of human bronchus or lung have shown that IBV are capable of causing severe lower respiratory tract infections; these frequently lead to fatal complications [9].…”