Bingqian Qu

• Doctor of Philosophy
• PostDoc Position at Paul Ehrlich Institut

The accessory protease transmembrane protease serine 2 (TMPRSS2) enhances severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake into ACE2-expressing cells, although how increased entry impacts downstream viral and host processes remains unclear. To investigate this in more detail, we performed infection assays in engineered cells prom...

Background & Aims 240 million people are chronically infected with hepatitis B virus (HBV) with very limited curative treatment option. HBV persistence requires maintenance of the covalently closed circular (ccc)DNA template. Furthermore, integration of HBV fragments driving HBV surface antigen (HBsAg) expression occurs frequently. While cccDNA tra...

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of effective HBV vaccination. During chronic infection, HBV forms two distinct templates responsible for viral transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host genome-integrated viral templates. Multiple ubiquitou...

Chronic infection with the human Hepatitis B Virus (HBV) is a major health problem. Virus persistence requires the establishment and maintenance of covalently closed circular (ccc) DNA, the episomal virus template in the nucleus of infected hepatocytes. Compared to replicative DNA intermediates (relaxed circular (rc) DNA), copy numbers of cccDNA in...

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, multiorgan dysfunction, and a high fatality rate between 12 and 30%. It is caused by SFTS virus (SFTSV), a novel Phlebovirus in family Bunyaviridae. Although the viral pathogenesis remains largely unknown, hemopoietic...

Four COVID-19 vaccines were developed, tested, and authorized early in Europe and the US. Comirnaty and Spikevax are mRNA-based, whereas Jcovden and Vaxzevria utilize adenoviral vectors (AdV). We described a hamster model of COVID-19 utilizing Wuhan-1 strain SARS-CoV-2, in which vaccine-associated immunopathogenesis can be induced by Alum-adjuvante...

The COVID-19 pandemic resulted in at least 776 million confirmed cases and 7 million deaths worldwide by the end of 2024 [...]

Current culture systems available for studying hepatitis D virus (HDV) are suboptimal. In this study, we demonstrate that hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) are fully permissive to HDV infection across various tested genotypes. When co-infected with the helper hepatitis B virus (HBV) or transduced to expr...

Lung immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for the ability to deal with infection. Using light sheet fluorescence microscopy of hamster lung slices in combination with virological, immunohistochemical, and RNA sequencing analyses, we show a wave of monocyte-derived macrophage (MDM) infiltration...

Current culture systems available for studying hepatitis D virus (HDV) are suboptimal. In this study, we demonstrate that hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) are fully permissive to HDV infection across various tested genotypes. When co- infected with the helper hepatitis B virus (HBV) or transduced to exp...

Compared with the other human H3N8 virus, the virus in the severe case has developed mutations e.g. in the HA, PB2 and NS1 proteins, Upon viral replication in the patient, a larger proportion of HA-G228S and the genesis of PB2-D153V correlated with severe pathogenesis.

Factors of the innate immune response to SARS-CoV-2 in the lungs are pivotal for the ability of the host to deal with the infection. In humans, excessive macrophage infiltration is associated with disease severity. Using 3D spatiotemporal analysis of optically cleared hamster lung slices in combination with virological, immunohistochemical and RNA...

The coronavirus (COVID-19) pandemic has been a global threat for the past three years at the time of writing, leading to more than 675 million confirmed cases and 6 [...]

Objectives A major goal of curative hepatitis B virus (HBV) treatments is the reduction or inactivation of intrahepatic viral covalently closed circular DNA (cccDNA). Hence, precise cccDNA quantification is essential in preclinical and clinical studies. Southern blot (SB) permits cccDNA visualisation but lacks sensitivity and is very laborious. Qua...

SARS-CoV-2 entry is promoted by both cell-surface TMPRSS2 and endolysosomal cathepsins. To investigate the impact of differentially routed virions on host and viral processes, lung epithelial cells expressing distinct combinations of entry factors were infected with authentic viruses. Entry route determined early rates of viral replication and tran...

Highly pathogenic influenza A virus H5 subtype remains a risk for transmission in humans. The H5N8 subtype has caused multiple outbreaks in poultry in Europe over the past few winters. During one recent outbreak in poultry in Astrakhan, workers on the farm were also infected. So far, little is known about how this virus evolves and adapts to infect...

Supplemental figures

HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test f...

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of an effective HBV vaccine. During chronic infection, HBV forms two distinct templates responsible for viral gene transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host-genome integrated viral templates. Multiple ubiqu...

Background and Aim: Hepatitis B virus (HBV) infection causes the majority of liver cancer cases worldwide. The infection cannot be cured by current therapeutics due to the persistence of covalently closed circular (ccc)DNA in the liver of infected individuals. It is unclear whether cccDNA persistence during antiviral therapy is: (1) due to ineffici...

Background & Aims Chronic hepatitis B virus (HBV) infection cannot be cured by current therapeutics due to their poor efficacy on covalently closed circular (ccc)DNA levels in the liver of infected individuals. Therefore, greater understanding the molecular determinants of cccDNA formation and persistence is required. One key issue is the extent to...

Background and Aims: The most physiological model for hepatitis D virus (HDV) infection is the primary human hepatocyte (PHH), yet their application is restricted by donor-to-donor variability and rapid ex vivo dedifferentiation. Reconstituting the HBV/HDV receptor, human sodium taurocholate cotransporting polypeptide (NTCP) renders hepatoma cells...

Hepatitis B virus (HBV) is the major cause of viral-associated liver disease. Persistent HBV infection is maintained by its episomal genome (covalently closed circular DNA, cccDNA), which acts as a template for viral transcripts. The formation of cccDNA is poorly characterised due to limited ability to quantify it accurately in the presence of repl...

Hepatitis B virus (HBV) chronic infection is a critical risk factor for hepatocellular carcinoma. The innate immune response to HBV infection is a matter of debate. In particular, viral escape mechanisms are poorly understood. Our study reveals that HBV RNAs are not immunostimulatory in immunocompetent myeloid cells. In contrast, HBV DNA from viral...

Human stem cell-derived hepatocyte-like cells (HLCs) offer an attractive platform to study liver biology. Despite their numerous advantages, HLCs lack critical in vivo characteristics, including cell polarity. Here, we report a stem cell differentiation protocol that uses transwell filters to generate columnar polarized HLCs with clearly defined ba...

Human infections with avian influenza viruses including H5, H7 and H9 hemagglutinin subtypes occur at a low rate. Among human infections with H7 viruses, regional outbreaks with H7N2, H7N3, H7N7 and H7N9 have been documented. Early in 2018, a human infection with a novel H7N4 avian influenza virus was reported in Jiangsu, China. This study is aimed...

Translation of abstract (English) Hepatitis B Virus (HBV) leads to chronic infection of the liver and is a risk factor for the development of cirrhosis and hepatocellular carcinoma. Virus persistence requires the establishment and maintenance of covalently closed circular (ccc)DNA, serving as the episomal template for transcription of viral genes...

HBV chronic infection is a critical risk factor for hepatocellular carcinoma. Although debated, the absence of innate immune response to HBV infection in hepatocytes is becoming the current view. However the underlying reasons are poorly understood. This study aims to define potential viral pathogen-associated molecular patterns (PAMPs) and the pat...

Viral hepatitis, the leading cause of liver diseases worldwide, is induced upon infection with hepatotropic viruses, including hepatitis A, B, C, D, and E virus. Due to their obligate intracellular lifestyles, culture systems for efficient viral replication are vital. Although basic and translational research on viral hepatitis has been performed f...

Introduction: Human infections with avian influenza viruses including H5 and H7 hemagglutinin subtypes occur, albeit at an occasional rate. Among human infections with H7 viruses, H7N2 (New York), H7N3 (Canada and Mexico), H7N7 (the Netherlands, UK, Italy) and H7N9 (global) cases were documented. However, other H7 subtype viruses have never been de...

Persistence of the human hepatitis B virus (HBV) requires the maintenance of covalently closed circular (ccc)DNA, the episomal genome reservoir in nuclei of infected hepatocytes. cccDNA elimination is a major aim in future curative therapies currently under development. In cell culture based in vitro studies, both hybridization- and amplification-b...

Background and aims: More than 200 million people worldwide are suffering from chronic Hepatitis B (HBV) infection without a curative therapeutic regimen available so far. One approach to control HBV replication is silencing transcription from covalently closed circular DNA (cccDNA). Efficient transcription requires the X protein (HBx) as a transcr...

BACKGROUND: Hepatitis B Virus (HBV) transcription from its template, covalently closed circular DNA (cccDNA), requires the HBV X protein (HBx)-induced degradation of the host restriction factor SMC5/6. A prerequisite for ubiquitin-dependent SMC5/6 degradation is binding of HBx to the DDB1-Cullin 4 ligase complex. Since neddylation of Cullin 4A, is...

Background & aims: Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy whereas HBV infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in co-infected cells. We investigated interact...

The PB1-F2 protein of influenza A virus has been considered a virulence factor, but its function in inducing apoptosis may be of disadvantage to viral replication. Host mechanisms to regulate PB1-F2-induced apoptosis remain unknown. We generated a PB1-F2-deficient avian influenza virus (AIV) H9N2 and found that the mutant virus replicated less effi...

Question: Hepatitis B and C virus (HBV, HCV) are a global health problem accounting for around 370 million chronically infected people worldwide. While HCV is inducing an interferon (IFN) response and is highly sensitive towards IFN treatment, the impact of the IFN system on the HBV life cycle is discussed controversially. Although HBV is regarded...

Infections with the human Hepatitis B (HBV) and Hepatitis D Virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide hNTCP. Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV indicating the requirement of additional HBV-specific factors. As an e...

Deoxynucleotide triphosphates (dNTPs) are essential for efficient hepatitis B virus (HBV) replication. Here, we investigated the influence of the restriction factor SAMHD1, a dNTP hydrolase (dNTPase) and RNase, on HBV replication. We demonstrated that silencing of SAMHD1 in hepatic cells increased HBV replication, while overexpression had the oppos...

Hepatitis B virus (HBV) enters hepatocytes via its receptor human sodium-taurocholate cotransporting polypeptide (hNTCP). So far, HBV infection has only been achieved in human hepatic cells reconstituted with hNTCP, but not in cells of mouse origin. Here, the first mouse liver cell line (AML12) is described, which gains susceptibility to HBV upon h...

Cells are equipped with pattern recognition receptors (PRRs) such as the Toll-like and RIG-I-like receptors that mount innate defenses against viruses. However, viruses have evolved multiple strategies to evade or thwart host antiviral responses. Viral inclusion bodies (IBs), which are accumulated aggregates of viral proteins, are commonly formed d...

Avian influenza viruses (AIV) replicate efficiently in guts of birds, and virus shedding is critical to viral transmission among birds and from birds to other species. In this study, we showed that an H9N2 viral strain, isolated from a human patient, caused typical influenza-like signs and illness including loss of body weight in Balb/c mice, and t...

Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered "mixing vessels" that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subse...

H9N2 subtype avian influenza viruses have evolved to cross species boundary and been able to infect humans, which has posed a potential threat for pandemic. In cases with an H9N2 infection, besides systemic and respiratory symptoms, diarrhea or other gastrointestinal symptoms were also reported. Little has been known about the susceptibility of hum...

Host responses in influenza virus infection are controlled by various signaling mechanisms. PI3 kinase (PI3K)/Akt signaling pathway is considered for cell survival and activated in influenza viral infection. One of the mechanisms for this activation is probably through viral nonstructural protein-1 directly interacting with PI3K. Our previous studi...

The avian influenza virus H9N2 subtype has circulated in wild birds, is prevalent in domestic poultry, and has successfully crossed the species boundary to infect humans. Phylogenetic analyses showed that viruses of this subtype appear to have contributed to the generation of highly pathogenic H5N1 viruses. Little is known about the host responses...

Signal transducer and activator of transcription 3 (STAT3) is constitutively active in approximately 50% of acute myeloid leukemia (AML) cases and mediates multiple cellular processes including cell resistance to apoptosis. Inhibition of constitutively active STAT3 has been shown to induce AML cell apoptosis. Our aim was to ascertain if sorafenib,...

The influenza A (H1N1) pandemic of 2009 is caused by a novel swine influenza virus, which has resulted in thousands of mortalities worldwide. Pulmonary failure due to over-induction of proinflammatory factors appeared to be the main cause in severe cases leading to death. To elucidate the pathogenesis of the novel H1N1 virus in humans, we infected...

The influenza A (H1N1) pandemic of 2009 is caused by a novel swine influenza virus, which has resulted in thousands of mortalities worldwide. Pulmonary failure due to over-induction of proinflammatory factors appeared to be the main cause in severe cases leading to death. To elucidate the pathogenesis of the novel H1N1 virus in humans, we infected...

Sunitinib (sunitinib malate; SU11248; SUTENT) is a novel multi-targeted receptor tyrosine kinase inhibitor currently approved for the treatment of metastatic renal cell carcinoma. To analyze the possible use of this compound in combination with immunotherapeutic approaches, we investigated the effects of sunitinib on the human peripheral T cells an...

Sorafenib, a novel drug for metastatic renal cancer, has broad-spectrum activity against multiple tyrosine kinases, including Raf-1, vascular endothelial growth factor receptor and platelet-derived growth factor receptor. However, little is known about its effects on the immune system. In this report, we examine the effects of sorafenib on the prol...