Xiaonan Zhang

University of Canberra · Faculty of Science and Technology

Probe-based nucleic acid enrichment represents an effective route to enhance the detection capacity of next-generation sequencing (NGS) in a set of clinically diverse and relevant microbial species. In this study, we assessed the effect of the enrichment-based sequencing on identifying respiratory infections using tiling RNA probes targeting 76 res...

Hepatitis B virus (HBV) developed highly intricates mechanisms exploiting host resources for its multiplication within a constrained genetic coding capacity. With the aid of a series of classical analytical methods such as ultrafiltration, and Southern and Northern blots, a general framework of HBV life cycle has been established. However, this pic...

Hepatitis B virus (HBV) is undoubtedly a master in exploiting host resources while evading host defense for its multiplication within a constrained genetic coding capacity. To further unravel these cunning strategies, a clear picture of virus-host interaction with key subcellular and molecular contexts is needed. Here, we describe a FISH protocol m...

Background and Aims The surface antigen of hepatitis B virus (HBsAg) serves as an important immune-modulatory factor in chronic hepatitis B (CHB). One aspect of such modulation may act through monocytes which are the major antigen presenting cells (APCs) taking up HBsAg. There is evidence for the encapsulation of hepatocellular miRNAs by HBsAg part...

The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major obstacle to curing chronic hepatitis B (CHB). Current cccDNA detection methods are mostly based on biochemical extraction and bulk measurements. They nevertheless generated a general sketch of its biological features. However, an understanding of the spatiotemporal...

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. Al...

The expression of various forms of hepatitis B virus (HBV) surface proteins regulates the release of mature virion, but whether they affect the release of other incomplete viral particles, such as naked capsid, is not clear. Here, by stable overexpression of large or middle/small hepatitis B surface proteins (LHBs, M/SHBs) in HepAD38 cells, we eval...

Hepatitis B virus exposure in children usually develops into chronic hepatitis B (CHB). Although hepatitis B surface antigen (HBsAg)-specific CD8+ T cells contribute to resolve HBV infection, they are preferentially undetected in CHB patients. Moreover, the mechanism for this rarely detected HBsAg-specific CD8+ T cells remains unexplored. We herein...

Aims Hepatitis B Virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC) in East Asia. Here we aimed to further investigate the abundance of viral antigen and DNA within HBV-related HCC and surrounding tissues at histological level. Method In addition to routine histopathology, in situ hybridization (ISH) of HBV DNA and i...

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The visualization of intrahepatic hepatitis B virus (HBV) DNA by in situ hybridization (ISH) has uncovered some interesting aspects of HBV life cycle at the single-cell level. In the current study, we intend to evaluate the reliability and robustness of this assay in the real-world clinical scenario and its relationship with currently available cli...

Through evolution, Hepatitis B Virus (HBV) developed highly intricate mechanisms exploiting host resources for its multiplication within a constrained genetic coding capacity. Yet a clear picture of viral hitchhiking of cellular processes with spatial resolution is still largely unsolved. Here, by leveraging bDNA-based fluorescence in situ hybridiz...

Hepatitis B virus (HBV) infection is a global public health problem that plagues approximately 240 million people. Chronic hepatitis B (CHB) often leads to liver inflammation and aberrant repair which results in diseases ranging from liver fibrosis, cirrhosis, to hepatocellular carcinoma. Despite its narrow species tropism, researchers have establi...

Metagenomic next-generation sequencing (mNGS) holds promise as a diagnostic tool for unbiased pathogen identification and precision medicine. However, its medical utility depends largely on assay simplicity and reproducibility. In the current study, we aimed to develop a streamlined Illumina and Oxford Nanopore-based DNA/RNA library preparation pro...

Pandemic SARS-CoV-2 has infected over 10 million people and caused over 500,000 mortalities. Vaccine development is in urgent need to stop the pandemic. Despite great progresses on SARS-CoV-2 vaccine development, the efficacy of the vaccines remains to be determined. Deciphering the interactions of the viral epitopes with their elicited neutralizin...

Metagenomic next generation sequencing (mNGS) holds promise as a diagnostic tool for unbiased pathogen identification and precision medicine. However, its medical utility depends largely on the assay simplicity and reproducibility. In the current study, we aimed to develop a streamlined Illumina and Oxford Nanopore-based DNA/RNA library preparation...

Pandemic SARS-CoV-2 has infected over 10 million people and caused over 500,000 mortalities. Vaccine development is in urgent need to stop the pandemic. Despite great progresses on SARS-CoV-2 vaccine development, the efficacy of the vaccines remains to be determined. Deciphering the interactions of the viral epitopes with their elicited neutralizin...

The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is critical for viral persistence in vivo. The lack of reliable, characterized and convenient small animal models for studying cccDNA persistence has long been a bottleneck for basic and translational research on HBV cure. A mouse model that can maintain intrahepatic cccDNA is u...

In December 2019, coronavirus disease 2019 (COVID-19), which is caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan (Hubei province, China)¹; it soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require...

Background: A virus community is the spectrum of viral strains populating an infected host, which plays a key role in pathogenesis and therapy response in viral infectious diseases. However automatic and dedicated pipeline for interpreting virus community sequencing data has not been developed yet. Results: We developed Quasispecies Analysis Pac...

Aims The visualisation of HBV DNA in liver sections of patients with chronic hepatitis B (CHB) in our previous report uncovered a mosaic distribution of viral antigens and nucleic acids. Here we aim to further explore the clinical utility of the in situ hybridisation (ISH) assay for HBV DNA. Method ISH of HBV DNA along with immunohistochemistry (I...

Background and aims: Interferon (IFN)-α, composed of numerous subtypes, plays a crucial role in immune defense. As the most studied subtype, IFN-α2 has been used for treating chronic hepatitis B virus (HBV) infection, with advantages of finite treatment duration and sustained virologic response, but its efficacy remains relatively low. This study...

At least three months have been passed since the outbreak of the severe acute respiratory disease, COVID-19 in Wuhan city, China in December 2019, caused by the infection of a novel coronavirus, SARS-CoV-2.1,2. Due to its rapid spread throughout China and abroad, knowledge sharing for both its epidemiology and clinic manifestations is urgently need...

Background and aim: Recently, several studies demonstrated that serum HBV RNA levels were associated with liver disease progression in patients with chronic hepatitis B virus (HBV) infection. This study aimed to determine whether serum HBV RNA levels were correlated with liver fibrosis. Methods: 319 treatment-naïve patients with chronic HBV infe...

Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD), which is a life threatening disease in certain children. The pathogenesis of EV71-caused HFMD is poorly defined due to the lack of simple and robust animal models with severe phenotypes that recapitulate symptoms observed in humans. Here, we generated the inf...

Chronic Hepatitis B Virus (HBV) infection is strongly associated with the progression of liver fibrosis, cirrhosis and hepatocellular carcinoma. Despite intensive study, the detailed mechanisms leading to HBV induced liver disease have not been fully elucidated. Previously, we reported a mosaic distribution of viral antigens and nucleic acids at si...

Life-long persistence of HBV replication and antigen expression in a recombinant cccDNA-based immunocompetent mouse model Abstrct: The cccDNA of Hepatitis B virus is critical for HBV persistence in vivo. The lack of reliable, characterized and convenient small animal models for studying cccDNA persistence has long been a bottleneck for basic and tr...

Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and...

Keep hepatocytes fresh Freshly isolated primary human hepatocytes (PHHs) quickly lose their identity and function in vitro, limiting their application in modeling infectious liver diseases and screening drugs. Xiang et al. describe a simple and effective five-chemical culture condition that can maintain the mature function of cultured PHHs for an e...

Although increasing evidence suggests the presence of extracellular HBV RNA species, their origin and molecular forms are still under debate. In addition to the infectious virions, HBV is known to secrete several species of incomplete viral particles, including hepatitis B surface antigen (HBsAg) particles, naked capsids, and empty virions, during...

Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes (CACs) in chronic hepatitis B patients Abstract: Extracellular HBV RNA has been detected in both HBV-replicating cell culture media and sera from chronic hepatitis B (CHB) patients, but its exact origin and composition remain controversial. Her...

Extracellular HBV RNA has been detected in both HBV-replicating cell culture media and sera from chronic hepatitis B (CHB) patients, but its exact origin and composition remain controversial. Here, we demonstrated that extracellular HBV RNA species were of heterogeneous lengths, ranging from the length of pregenomic RNA to a few hundred nucleotides...

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), existing in hepatocyte nuclei as a stable minichromosome, plays a central role in the life cycle of the virus and permits the persistence of infection. Despite being essential for HBV infection, little is known about the molecular mechanisms of cccDNA formation, regulation and degrada...

Background: The natural history of chronic HBV infection was divided into four phases. Patients in the inactive carrier status (IC) and immune tolerant (IT) phase had normal ALT levels but huge different viral loads. The mechanism underlying low viral replication status in IC phase is unknown. Methods: We determined the intrahepatic transcriptom...

Background We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of ser...

Background The current clinical practice on chronic hepatitis B (CHB) requires better on-treatment monitoring of viral persistence. Quantified assays for hepatitis B surface antigen (HBsAg) and core-related antigen (HBcrAg) hold promise for further optimization of therapy. Here, we aimed to characterize HBcrAg during the natural course of CHB. Met...

Hepatitis B virus (HBV) infection has been one of the most important public health problems, however, no complete cure is currently available. Although interferon (IFN)-α has been clinically used as a drug for chronic hepatitis B therapy because of its advantages including a higher rate of HBsAg/HBeAg seroconversion and a lower rate of recurrence a...

Interferon-alpha (IFN-α) therapy of chronic hepatitis B (CHB) patients is constrained by limited response and side effects. We described a panel of circulating microRNAs (miRNAs) which could potentially predict outcome of IFN-α therapy. Here, we report development of a simplified scoring model for personalized treatment of CHB patients. 112 CHB pat...

While chronic hepatitis B remains a global public health problem, the detailed spatiotemporal dynamics of the key molecular events leading to the multiplication and egress of hepatitis B virus (HBV) are still largely unclear. Previously, we developed a chromogenic in situ hybridization assay for detection of HBV RNA, DNA and covalently closed circu...

Establishment of a fluorescent in situ hybridization assay for imaging hepatitis B virus nucleic acids in cell culture models

Background: Liver biopsy is the gold standard to assess pathological features (e.g. inflammation grades) for hepatitis B virus infected patients, although it's invasive and traumatic; meanwhile, several gene profiles of chronic hepatitis B (CHB) have been separately described in relatively small HBV-infected samples. We aimed to analyze correlatio...

Although hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF), the mechanisms underlying liver fibrotic progression remain unclear. Here, we investigated the gene expression profiles of HBV-related LF patients. Whole genome expression arrays were used to detect gene expression in liver biopsy samples from chronically HBV in...

Hepatitis B virus (HBV) infection is a major health problem worldwide. Recent evidence suggests that some viruses can manipulate the infection process by packing specific viral and cellular components into exosomes, small nanometer-sized (30-150 nm) vesicles secreted from various cells. However, the impact of HBV replication on the content of exoso...

Conclusion: PRMT5 restricts HBV replication via two-part mechanisms including epigenetic suppression of cccDNA transcription and interference with pgRNA encapsidation. These findings improve the understanding of epigenetic regulation of HBV transcription and host-HBV interaction, thus provide new insights into targeted therapeutic intervention. Th...

Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV l...

Plasmablastic lymphoma is a rare and aggressive B cell lymphoma that is considered to be strongly associated with HIV infection. This article explores the histological morphology and immunohistochemical characteristics of HIV/AIDS-related plasmablastic lymphoma with the goal of improving the diagnosis and treatment of this rare tumor. According to...

Persistent hepatitis B virus (HBV) infection is established by the formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver. Very little is known about the intrahepatic distribution of HBV cccDNA in infected patients, particularly at the single-cell level. Here, we established a highly sensitive and specific ISH ass...

Chlamydiae, obligate intracellular bacteria, are associated with a variety of human diseases. Chlamydial life cycle undergoes a bipahsic development: replicative reticulate bodies' phase (RBs) and infectious elementary bodies's phase (EBs). In the end of the chlamydial intracellular life cycle, EBs has to be released to the surrounded cells. Theref...

HCV infections are a major global health concern. Although direct acting antiviral agents have significantly improved the response rate of anti-HCV therapy, they also suffered from drug resistance, unfavorable pharmacokinetic profiles and high costs. Thus, it is still highly desirable to develop new anti-HCV therapeutics. Herein a novel anti-HCV be...

Chronic hepatitis B (CHB) remains a global health problem. Therapeutic vaccination has been successfully employed to treat a subpopulation of CHB patients. Personalized treatment can not only improve therapeutic efficacy, but also decrease the cost of medical care. Since microRNAs (miRNAs) are highly conserved and are involved in many cellular proc...

During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepatitis B (CHB) is shown to correlate with an impaire...

Hepatitis B virus (HBV) persistent infection is associated with ineffective immune response for the clearance of virus. Immunomodulators represent an important class of therapeutics, which potentially could be beneficial for the treatment of HBV infection. The particulate yeast-derived glucan (PYDG) has been shown to enhance the innate and adaptive...