Over 240 million people worldwide are chronically infected with Hepatitis B Virus (HBV), a hepatotropic DNA virus with an evolutionary root of over 400 million years. Persistent HBV infection exhibits distinct and diverse phases of disease, from minimal liver pathology to fulminant Hepatitis, that vary in duration and severity among individuals. Although huge progress has been made in HBV research which has yielded an effective prophylactic vaccine and potent antiviral therapy, our understanding of its virology and immunobiology is still far from complete. For example, the recent re-discovery of serum HBV RNA in chronic Hepatitis B (CHB) patients has led to the proposal of noncanonical viral particles such as RNA virion and capsid-derived immune complex (Capsid-Antibody-Complexes, CACs) that contradict long-established basic theory. Furthermore, the existence of capsid-derived immune complex may hint at novel mechanism of HBV-induced liver disease. Here, we summarize the past and recent literature on HBV-induced immune complex. We propose that the release of capsid-derived particles by HBV has its deep evolutionary origin, and the associated complement activation serves as an indispensable trigger for intrahepatic damage and a catalyst for further cell-mediated immunopathology.

Developing a quantum dot (QD) nanobeads-based lateral-flow assay (LFA) is of great importance for achieving ultrasen-sitive, quantitative, and rapid testing of clinical specimens at the point-of-care. However, the QD nanobeads currently used in LFA still have drawbacks such as large particle size, which leads to high background, easy aggregation, and poor fluidity. To address these issues, a promising strategy is to utilize plasmonic energy transfer from gold nanoparticles (AuNPs) to QDs in order to create smaller size and brighter fluorescent QD nanobeads, without simply increasing the amount of QDs encapsulated in the nanobeads. In this study, we prepared the plasmon-enhanced quantum dot nano-beads (PEQNB) by encapsulating AuNPs and QDs into polymer nanobeads using the versatile emulsion-solvent evapora-tion method. We were able to detect as low as ~4347 PEQNBs nanoparticles using a gel imager, which is 14.6 times brighter than the QD nanobeads of a similar size. Compared to QD nanobeads of similar size, the PEQNB-based LFA for interleukin-6 detection exhibited higher fluorescent signal and lower background. The detection limit of PEQNB-based LFA was 1.63-fold higher than that of QD nanobeads. Furthermore, compared to larger-sized QD nanobeads with aver-age diameter of 131.1nm, PEQNB with average diameter of 78.6 nm based LFA exhibited similar levels of fluorescence intensity, but 1.55-fold lower background signal and 1.44-fold lower detection limits. This work demonstrates that opti-mized plasmon-enhanced QD nanobeads can further increase the sensitivity and lower the background signals of ultra-sensitive QD nanobeads-based LFA for disease diagnosis at point-of-care.