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.
Plasma lipoproteins and apoproteins were compared among Chinese and American controls and non-insulin-dependent diabetic (NIDDM) subjects in the same laboratory. Apoprotein AI concentrations in Chinese subjects, both NIDDM subjects and controls (men, 147 and 158 mg/dl, respectively), were significantly higher than those in American subjects (men, 104 and 124 mg/dl, respectively). Apoprotein AII concentrations, however, were comparable between Chinese and American subjects. Chinese NIDDM subjects had lower high-density lipoprotein cholesterol (HDLC), higher low-density lipoprotein cholesterol (LDLC), and higher apoprotein B levels than Chinese controls. Chinese subjects with NIDDM had HDLC and LDLC levels similar to those of American controls but trends of higher HDLC and lower LDLC compared with American subjects with NIDDM. These differences may in part explain the relatively higher incidence of atherosclerotic vascular disease in Americans.
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