Guangxiang Luo's research while affiliated with University of Alabama at Birmingham and other places

Publications (65)

Article
Full-text available
Background As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe...
Article
Full-text available
Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, resulting in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV vaccine is effective to prevent new HBV infection but does not offer therapeutic benefit to hepatitis B patients. Neither are current antiviral drugs curative of chronic hepatitis B. A more...
Article
Full-text available
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino-acid fragment of the 1,273-amino-acid S-protein protomer. The RBD is the primary...
Preprint
Full-text available
As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective...
Preprint
Full-text available
The SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates viral entry into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. The RBD is the primary SARS-CoV-2 neutralizing e...
Preprint
Full-text available
The SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates entry of SARS-CoV-2 into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. Antibodies to the RBD domain of SARS-CoV...
Article
Emerging viral infections continue to pose a major threat to global public health. In 1997, a highly pathogenic avian influenza A (H5N1) virus was found to directly spread from poultry to humans unlike previously reported transmission routs of human‐to‐human and livestock‐to‐human, stirring a grave concern for a possible influenza pandemic. This ar...
Article
Zika virus (ZIKV) nonstructural protein 5 (NS5) is a multifunctional protein possessing methyltransferase and RNA-dependent RNA polymerase activities. In the present study, we have carried out an extensive mutagenesis analysis to determine the importance of nuclear localization sequences (NLS) of NS5 in its nuclear accumulation and ZIKV replication...
Article
Full-text available
Hepatitis B virus (HBV) is a common cause of liver diseases, including chronic hepatitis, steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HBV chronically infects about 240 million people worldwide, posing a major global health problem. The current standard antiviral therapy effectively inhibits HBV replication but does not elimi...
Chapter
Apolipoprotein E (apoE) plays dual functions in the HCV life cycle by promoting HCV infection and virion assembly and production. ApoE is a structural component on the HCV envelope. It mediates HCV cell attachment through specific interactions with the cell surface receptors such as syndecan-1 (SDC-1) and SDC-2 heparan sulfate proteoglycans (HSPGs)...
Article
Full-text available
Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as an important human viral pathogen, causing congenital malformation including microcephaly among infants born to mothers infected with the virus during pregnancy. Phylogenetic analysis suggested that ZIKV can be classified into African and Asian lineages. In this study, we have dev...
Article
HBV research has been greatly hampered by the lack of robust cell culture and small animal models of HBV infection and propagation. The discovery of NTCP as an HBV receptor has greatly impacted the field of HBV research. Although HBV infection of NTCP-expressing human and murine hepatocyte cell lines has been demonstrated, its replication in cell c...
Article
Previous studies have shown that apolipoprotein C1 (apoC1)-specific antibodies precipitated hepatitis C virus (HCV) and neutralized HCV infectivity, suggesting that apoC1 is a HCV component. However, the importance of apoC1 in the HCV life cycle has not been experimentally examined. In the present study, we sought to determine the role of apoC1 in...
Article
Full-text available
Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the liver. A more thorough understanding of HCC pathogenesis will provide novel targets for development of cancer drugs to effectively treat HCC. To further this goal, we carried out a proteomic profiling of HCC cell lines Huh-7.4 and Huh-7.5. These two cell lines were deri...
Article
Full-text available
Hepatitis C virus (HCV) requires multiple receptors for its attachment to and entry into cells. Our previous studies found that human syndecan-1 (SDC-1), SDC-2, and T cell immunoglobulin and mucin domain-containing protein 1 (TIM-1) are HCV attachment receptors. Other cell surface molecules, such as CD81, Claudin-1 (CLDN1), Occludin (OCLN), SR-BI,...
Article
Full-text available
Importance: TIM family proteins were recently found to enhance infection of many different viruses including several members of the Flaviviridae family. However, their importance in HCV infection has not been experimentally examined. The TIM family proteins include three members in humans, TIM-1, TIM-3, and TIM-4. The findings derived from our stu...
Article
Recent studies demonstrated that transgenic mice expressing key human HCV receptors are susceptible to HCV infection albeit at very low efficiency. Robust mouse models of HCV infection and replication are needed to determine the importance of host factors in HCV replication, pathogenesis, and carcinogenesis as well as to facilitate the development...
Article
Full-text available
The hepatitis C virus (HCV) is one of the leading causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinomas and infects approximately 170 million people worldwide. Although several reporter systems have been developed, many shortcomings limit their use in the assessment of HCV infections. Here, we report a real-time live-cell repor...
Article
Full-text available
Unlabelled: Hepatitis C virus (HCV) entry involves binding to cell surface heparan sulfate (HS) structures. However, due to the lipoprotein-like structure of HCV, the exact contribution of virion components to this interaction remains controversial. Here, we investigated the relative contribution of HCV envelope proteins and apolipoprotein E in th...
Article
Full-text available
Our previous studies demonstrated that the cell culture-grown hepatitis C virus of genotype 2a (HCVcc) uses apolipoprotein E (apoE) to mediate its attachment to the surface of human hepatoma Huh-7.5 cells. ApoE mediates HCV attachment by binding to the cell surface heparan sulfate (HS) which is covalently attached to the core proteins of proteoglyc...
Article
Full-text available
Our recent studies demonstrated that apolipoprotein E mediates cell attachment of hepatitis C virus (HCV) through interactions with the cell surface heparan sulfate (HS). HS is known to covalently attach to core proteins to form heparan sulfate proteoglycans (HSPGs) on the cell surface. The HSPG core proteins include the membrane-spanning syndecans...
Article
Full-text available
The PI3K-AKT signaling pathway plays an important role in cell growth and metabolism. Here we report that HCV transiently activates the PI3K-AKT pathway. This activation was observed as early as 15 minutes post-infection, peaked by 30 minutes, and became undetectable at 24 hours post-infection. The activation of AKT could also be mediated by UV-ina...
Article
Full-text available
Recent genetic studies suggested that viral nonstructural (NS) proteins play important roles in morphogenesis of flaviviruses, particularly hepatitis C virus (HCV). Adaptive and compensatory mutations occurring in different NS proteins were demonstrated to promote HCV production in cell culture. However, the underlying molecular mechanism of NS pro...
Article
Full-text available
Viruses are known to use virally encoded envelope proteins for cell attachment, which is the very first step of virus infection. In the present study, we have obtained substantial evidence demonstrating that hepatitis C virus (HCV) uses the cellular protein apolipoprotein E (apoE) for its attachment to cells. An apoE-specific monoclonal antibody wa...
Article
Hepatitis C virus (HCV) infection is the leading cause of chronic liver diseases worldwide. There is no vaccine to prevent HCV infection. Current standard of care (SOC) for hepatitis C is pegylated interferon-α (pegIFN-α) in combination with ribavirin (RBV). However, the efficacy of pegIFN-α and RBV combination therapy is less than 50% for genotype...
Article
Full-text available
We have recently demonstrated that human apolipoprotein E (apoE) is required for the infectivity and assembly of hepatitis C virus (HCV) (K. S. Chang, J. Jiang, Z. Cai, and G. Luo, J. Virol. 81:13783-13793, 2007; J. Jiang and G. Luo, J. Virol. 83:12680-12691, 2009). In the present study, we have determined the molecular basis underlying the importa...
Article
Full-text available
Our previous studies have found that hepatitis C virus (HCV) particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. Studies by others, however, suggested that both microsomal transfer protein (MTP) and apoB are important for HCV production. To define the roles of apoB and apoE in the HCV life...
Article
RNA replication of HCV occurs in the multiprotein complexes associated with the endoplasmic reticular (ER) membranes. The HCV NS3 to NS5B proteins are necessary and sufficient for HCV RNA replication in the cell, but cellular proteins in the HCV replication complex (RC) have not been determined. Several methods have been used to isolate the HCV RC,...
Article
Unlabelled: Hepatitis C virus (HCV) is a major human pathogen that causes serious illness, including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Using a mass spectrometry-based proteomics approach, we have identified 175 proteins from a cell culture supernatant fraction containing the HCV genotype 2a (JFH1) virus, among w...
Article
Full-text available
Recent advances in reverse genetics of hepatitis C virus (HCV) made it possible to determine the properties and biochemical compositions of HCV virions. Sedimentation analysis and characterization of HCV RNA-containing particles produced in the cultured cells revealed that HCV virions cover a large range of heterogeneous densities in sucrose gradie...
Article
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Serum amyloid A (SAA) is an acute-phase protein induced by a variety of inflammatory stimuli, including bacterial and viral infections. SAA was recently found to function as an opsonin for gram-negative bacteria. We report here that SAA inhibited hepatitis C virus (HCV) infection in cultured cells. SAA reduced HCV infectivity in a dose-dependent ma...
Article
Full-text available
Development of full-length hepatitis C virus (HCV) RNAs replicating efficiently and producing infectious cell-cultured virions, HCVcc, in hepatoma cells provides an opportunity to characterize immunogenic domains on viral envelope proteins involved in entry into target cells. A panel of immunoglobulin G1 human monoclonal antibodies (HMAbs) to three...
Article
Full-text available
Hepatitis C virus (HCV) infection causes chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. The underlying mechanisms of chronic HCV infection and IFN-based therapies, however, have not been defined. Protein kinase R (PKR) was implicated in the control of HCV replication and mediation of IFN-induced antiviral...
Article
Our earlier work found that the polypyrimidine tract-binding protein (PTB) specifically interacts with the poly(U/C) tract of the hepatitis C virus (HCV) 3' untranslated region (3'UTR) [Luo, G., 1999. Cellular proteins bind to the poly(U) tract of the 3' untranslated region of hepatitis C virus RNA genome. Virology 256, 105-118]. We report here tha...
Article
Full-text available
Hepatitis C virus (HCV) chronically infects approximately 170 million people worldwide, with an increased risk of developing cirrhosis and hepatocellular carcinoma. The study of HCV replication and pathogenesis has been hampered by the lack of an efficient stable cell culture system and small-animal models of HCV infection and propagation. In an ef...
Article
The viral RNA plays multiple roles during replication of RNA viruses, serving as a template for complementary RNA synthesis and facilitating the assembly of the viral replicase complex. These roles are coordinated by cis-acting regulatory elements, such as promoters and replication enhancers (REN). To test if these RNA elements can be used by relat...
Article
Full-text available
Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is the virus-encoded RNA-dependent RNA polymerase (RdRp) essential for HCV RNA replication. An earlier crystallographic study identified a rGTP-specific binding site lying at the surface between the thumb domain and the fingertip about 30 A away from the active site of the HCV RdRp (S. Bressan...
Article
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Hepatitis C virus (HCV) nonstructural protein 3 (NS3) possesses multiple enzyme activities. The N-terminal one-third of NS3 primarily functions as a serine protease, while the remaining two-thirds of NS3 serve as a helicase and nucleoside triphosphatase. Whether the multiple enzyme activities of NS3 are functionally interdependent and/or modulated...
Article
The hepatitis C virus (HCV) is a major cause of liver disease worldwide. The understanding of the viral life cycle has been hampered by the lack of a satisfactory cell culture system. The development of the HCV replicon system has been a major advance, but the system does not produce virions. In this study, we constructed an infectious HCV genotype...
Article
Full-text available
The sensitivities and specificities of an immunofluorescence assay and an enzyme immunoassay for detection of antibodies specific for severe acute respiratory syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS cases. The appearance and persistence of SARS-CoV-specific antibodies were assessed, with immunoglobulin G dete...
Article
Replication of nearly all RNA viruses depends on a virus-encoded RNA-dependent RNA polymerase (RdRp). Our earlier work found that purified recombinant hepatitis C virus (HCV) RdRp (NS5B) was able to initiate RNA synthesis de novo by using purine (A and G) but not pyrimidine (C and U) nucleotides (G. Luo et al., J. Virol. 74:851-863, 2000). For most...
Article
Biochemical studies revealed that nonstructural proteins of hepatitis C virus (HCV) interacted with each other and were associated with intracellular membranes. The goals of this study were to determine whether nonstructural viral proteins are colocalized at specific intracellular sites where HCV RNA is replicated and to identify the virus componen...
Article
Sequences of the untranslated regions at the 5' and 3' ends (5'UTR and 3'UTR) of the hepatitis C virus (HCV) RNA genome are highly conserved and contain cis-acting RNA elements for HCV RNA replication. The HCV 5'UTR consists of two distinct RNA elements, a short 5'-proximal stem-loop RNA element (nucleotides 1 to 43) and a longer element of interna...
Article
In an effort to determine the cause of non-A-E hepatitis, a retrospective study was undertaken on a group of patients with hepatitis but without serological infection markers of hepatitis viruses A-E. A total of 60 patients admitted to Beijing Ditan Hospital during the period of September 1997 and September 1999 were chosen for this study. These pa...

Citations

... In agreement with other studies [34,36,[40][41][42], we observed inhibition of 3CL protease by EGCG and ECG. Consistent with earlier studies showing inhibition of SARS-CoV-2 entry by EGCG [43,44], we observed inhibition at the entry stage of the viral life cycle. ...
... B.1.1.529 has 32 mutations on the spike protein in comparison with Delta variant (B.1.617.2) that had 9 mutations on the spike protein [10]. ...
... This inhibition led to a 90% decrease in HBV cccDNA, DNA and HBe (another, core-derived, HBV protein secreted into the extracellular environment) levels in infected cells [83]. Furthermore, the use of Abs targeting LDL-R, or of siRNA and CRISPR/Cas9 inducing the knockout of the receptor yielded the same results, highlighting the role of LDL-R as a cofactor in HBV entry and explaining the role of ApoE on the particles in mediating ligand binding to the receptor [84]. HBV S has also been reported to interact with glycosaminoglycans (GAGs), facilitating the attachment of HBV to cells [85,86]. ...
... Subunit vaccines are another rapidly developing area in the development of COVID-19 prevention tools [20][21][22]. Currently, a number of subunit vaccines based on the spike (S) protein or its fragments are undergoing clinical trials [7,23,24]. ...
... Epigallocatechin-3-gallat (EGCG, Fig. 1A), a major component of the green tea extract, is currently in the limelight, as it shows pronounced inhibitory activity against various types of viruses, especially with positive-sense single-stranded RNA genomes [1]. Discussions on EGCG applicability for SARS-CoV-2 treatment or prevention are mostly grounded by the results of lentiviral systembased assays [2]. Direct evidence for EGCG activity against SARS-CoV-2 is limited [3], and detailed experiments with the live virus and various treatment schemes are much needed. ...
... All currently known platforms used for vaccine development have been used to produce vaccines against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) including inactivated virus [1,2], recombinant proteins and synthetic peptides [3][4][5], vector vaccines [6,7], DNA-based constructs [8,9], and RNA-based constructs [10,11]. Each has its advantages and disadvantages. ...
... Detection of SARS-CoV-2-specific antibodies are observed early in the convalescent period, and appear to persist for at least 5-6 months [6][7][8]. While many commercial assays detect antibodies to the highly conserved virus nucleocapsid (NP) [9], it is antibodies to the spike protein, and specifically the receptor-binding domain (RBD) with its role in virus attachment and cell entry, where a correlation has been made with neutralisation [10]. Antibody detectability has broadly been associated with disease severity [11]. ...
... In preliminary preclinical studies, FINLAY-FR-02 elicited strong neutralizing anti-RBD antibodies (Valdés-Balbín et al., 2021), indicating the product potential as a vaccine candidate. Here we evaluate the safety profile of FINLAY-FR-02 in a repeat-dose toxicity and local tolerance study in Sprague Dawley rats; this versatile and well-characterized model in vaccine toxicology studies (Forster, 2012) has been used in preclinical studies on COVID-19 vaccines (Kandeil et al., 2021;Brian et al., 2020;. ...
... In human history, various pathogenic microorganisms such as bacteria, viruses, protozoa, and fungi have been the leading cause of morbidity and mortality around the globe (Luo and Gao, 2020). To combat with these pathogen related infections, many generations of antibiotics have been developed. ...
... Ivermectin is an FDA-approved anti-parasitic drug for the prevention of heartworm disease in certain animals such as cattle, dogs, and horses. Studies have shown the efficacy of IVM against viruses such as Zika virus and IAV [78,79]. IVM is proposed to disrupt the host importin heterodimer complex (IMPα/β1) for the transport of SARS-CoV-2 proteins such as NSP12-RdRp during infection, thereby hijacking viral replication [80,81]. ...