Serum levels of preS antigen (HBpreSAg) in chronic hepatitis B virus infected patients

Lian, Min; Zhou, Xu; Wei, Lai; Qiu, Shaowei; Zhou, Tong; Li, Lanfen; Gu, Xiaocheng; Luo, Ming; Zheng, Xiaofeng

doi:10.1186/1743-422x-4-93

Cited by 5 publications

(8 citation statements)

References 34 publications

(24 reference statements)

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“…Next, we set out to purify the preS VLP from supernatant of the transfected 293T cells. Recombinant preS was also produced in E. coli (Lian et al, 2007) (Fig. S1) and was used to generate specific polyclonal antibodies.…”

Section: Resultsmentioning

confidence: 99%

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A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibodies and T cell responses in mice

et al. 2018

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The preS antigen of hepatitis B virus (HBV) corresponds to the N-terminal polypeptide in the large (L) antigen in addition to the small (S) antigen. The virus-like particle (VLP) of the S antigen is widely used as a vaccine to protect the population from HBV infection. The presence of the S antigen and its antibodies in patient blood has been used as markers to monitor hepatitis B. However, there is very limited knowledge about the preS antigen. We generated a preS VLP that is formed by a chimeric protein between preS and hemagglutinin (HA), and the matrix protein M1 of influenza virus. The HBV preS antigen is displayed on the surface of preS VLP. Asn112 and Ser98 of preS in VLP were found to be glycosylated and O-glycosylation of Ser98 has not been reported previously. The preS VLP shows a significantly higher immunogenicity than recombinant preS, eliciting robust anti-preS neutralizing antibodies. In addition, preS VLP is also capable of stimulating preS-specific CD8 and CD4 T cell responses in Balb/c mice and HBV transgenic mice. Furthermore, preS VLP immunization provided protection against hydrodynamic transfection of HBV DNA in mice. The data clearly suggest that this novel preS VLP could elicit robust immune responses to the HBV antigen, and can be potentially developed into prophylactic and therapeutic vaccines.

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Section: Resultsmentioning

confidence: 99%

“…In order to investigate humoral immunogenicity of preS VLP, Balb/c mice were immunized each with 10 μg of preS VLP total protein, or recombinant preS (Lian et al, 2007) with alum adjuvant, respectively (Fig. 3A).…”

Section: Resultsmentioning

confidence: 99%

A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibodies and T cell responses in mice

et al. 2018

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“…In addition to the HBsAg and its specific antibody and other commonly used markers, the pre-S antigens and anti-pre-S antibodies may be used as serological markers for HBV infection. 109,110 The pre-S antigens are reactive antigens located on the L and M proteins. It has been reported that the proportions of the L and M proteins differ across the different phases of HBV infection; for example, patients in the inactive carrier (IC) phase had significantly lower ratios of the L and M proteins compared to patients in the acute or chronic phases.…”

Section: Pre-s Antigens and Specific Antibodies As Diagnostic Markers For Hbv Infectionmentioning

confidence: 99%

“…-7 of 14 and detected all the pre-S antigens in serum with higher sensitivity. 110 Pre-S antigens are highly immunogenic and can elicit the production of anti-pre-S antibodies. Studies have indicated that antibodies against pre-S1 proteins may serve as protective antibodies and contribute to the elimination of hepatitis B, and the positive result of anti-pre-S1 antibodies suggested recovery from chronic hepatitis B.…”

Section: Pre-s Antigens and Specific Antibodies As Diagnostic Markers For Hbv Infectionmentioning

confidence: 99%

Hepatitis B virus pre‐S region: Clinical implications and applications

Sun

Chang

Yan

et al. 2020

Reviews in Medical Virology

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Hepatitis B virus (HBV) infection is a major threat to global public health, which can result in many acute and chronic liver diseases. HBV, a member of the family Hepadnaviridae, is a small enveloped DNA virus containing a circular genome of 3.2 kb. Located upstream of the S-open-reading frame of the HBV genome is the pre-S region, which is vital to the viral life cycle. The pre-S region has high variability and many mutations in the pre-S region are associated with several liver diseases, such as fulminant hepatitis (FH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). In addition, the pre-S region has been applied in the development of several pre-S-based materials and systems to prevent or treat HBV infection. In conclusion, the pre-S region plays an essential role in the occurrence, diagnosis, and treatment of HBV-related liver diseases, which may provide a novel perspective for the study of HBV infection and relevant diseases. K E Y W O R D Shepatitis B virus (HBV), pre-S mutants, occult HBV infection | INTRODUCTIONHepatitis B is a non-negligible, life-threatening liver infection caused by the hepatitis B virus (HBV). It can progress to chronic infection, putting infected people at enormous risk of developing liver cirrhosis (LC), hepatocellular carcinoma (HCC), and even causing death. 1 A total of 257 million people worldwide have been chronically infected with HBV as of 2016, and it results in an estimated 887,000 deaths annually. 2 Hepatitis B has imposed huge burdens on many countries, and it remains a global public health problem that requires an urgent response.HBV belongs to the family Hepadnaviridae and is a small enveloped DNA virus. The viral genome is a partially double-stranded DNA with approximately 3200 base pairs. Based on the sequence divergence of the full HBV genome, 10 genotypes (A to J) and several subtypes of HBV have been identified, with different geographical distributions. 3 Four partially overlapping open-reading frames (ORFs) in the viral genome (pre-S/S, pre-C/C, P, and X) are responsible for encoding essential proteins for the viral life cycle. Among them, the pre-S/S ORF encodes three enveloped/surface proteins, that is, Large (L), Middle (M), and Small (S) proteins. 4 In fact, in addition to encoding surface proteins, the pre-S domain is reported to have many other important functions in the HBV life cycle, such as mediating HBV infection, forming viral particles, and inducing host immune responses. 5 The pre-S region has high variability, and mutations of the pre-S region have been confirmed to be related to several different acute and chronic liver diseases, which are of great clinical significance. 6 Moreover, the pre-S domain has displayed good

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“…During HBV infection, both infected and uninfected hepatocytes exhibit changes in death receptor expression and in their susceptibility to death [Kolios et al, ; Liang et al, ]. The fact that the envelope proteins are extensively secreted by infected cells (levels in serum are detected up to 80 μg/ml) provides a possible explanation for the effects [Lian et al, ; Chen et al, ]. The exposure of uninfected cells to the extracellular preS1/2 could trigger apoptosis signals in the hepatocytes and thus contribute substantially to disease pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Programmed hepatocytes cell death associated with FLIP downregulation in response to extracellular PreS1/2

Rojas

Barboza

Terán-Ángel

et al. 2013

Journal of Medical Virology

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Chronic hepatitis B virus (HBV) infection involves liver damage resulting in continuous cell injury and death. During HBV infection, hepatocytes exhibit changes in death receptor expression and in their susceptibility to death. These changes are observed not only in infected cells but also in bystander cells. Because excess viral surface protein (HBsAg) is secreted in large amounts as soluble particles containing preS proteins, the role of soluble preS1/2 in hepatocyte (HepG2) death modulation is an important issue to be explored. An increase of cell death induced by preS1/2 was observed. Also, cell death was associated with the down-regulation of FLIP and activation of caspase 8, caspase 9, and BID. Additionally, hepatocytes exhibited a sensitization to death mediated by the Fas receptor. These results, may contribute to understanding the role of envelope proteins (preS1/2) in the pathogenesis of HBV infection.

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Serum levels of preS antigen (HBpreSAg) in chronic hepatitis B virus infected patients

Cited by 5 publications

References 34 publications

A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibodies and T cell responses in mice

A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibodies and T cell responses in mice

Hepatitis B virus pre‐S region: Clinical implications and applications

Programmed hepatocytes cell death associated with FLIP downregulation in response to extracellular PreS1/2

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