• Title/Summary/Keyword: hepatitis E virus

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Low Frequency of Precore Mutants in Anti-Hepatitis B e Antigen Positive Subjects with Chronic Hepatitis B Virus Infection in Chennai, Southern India

  • Shanmugam, Saravanan;Velu, Vijayakumar;Nandakumar, Subhadra;Madhavan, Vidya;Shanmugasundaram, Uma;Shankar, Esaki Muthu;Murugavel, Kailapuri G.;Balakrishnan, Pachamuthu;Kumarasamy, Nagalingeswaran;Solomon, Suniti;Thyagarajan, Sadras Panchatcharam
    • Journal of Microbiology and Biotechnology
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    • v.18 no.10
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    • pp.1722-1728
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    • 2008
  • The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBe, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.

Construction and Characterization of an Anti-Hepatitis B Virus preS1 Humanized Antibody that Binds to the Essential Receptor Binding Site

  • Wi, Jimin;Jeong, Mun Sik;Hong, Hyo Jeong
    • Journal of Microbiology and Biotechnology
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    • v.27 no.7
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    • pp.1336-1344
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    • 2017
  • Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma. With recent identification of HBV receptor, inhibition of virus entry has become a promising concept in the development of new antiviral drugs. To date, 10 HBV genotypes (A-J) have been defined. We previously generated two murine anti-preS1 monoclonal antibodies (mAbs), KR359 and KR127, that recognize amino acids (aa) 19-26 and 37-45, respectively, in the receptor binding site (aa 13-58, genotype C). Each mAb exhibited virus neutralizing activity in vitro, and a humanized version of KR127 effectively neutralized HBV infection in chimpanzees. In the present study, we constructed a humanized version (HzKR359-1) of KR359 whose antigen binding activity is 4.4-fold higher than that of KR359, as assessed by competitive ELISA, and produced recombinant preS1 antigens (aa 1-60) of different genotypes to investigate the binding capacities of HzKR359-1 and a humanized version (HzKR127-3.2) of KR127 to the 10 HBV genotypes. The results indicate that HzKR359-1 can bind to five genotypes (A, B, C, H, and J), and HzKR127-3.2 can also bind to five genotypes (A, C, D, G, and I). The combination of these two antibodies can bind to eight genotypes (A-D, G-J), and to genotype C additively. Considering that genotypes A-D are common, whereas genotypes E and F are occasionally represented in small patient population, the combination of these two antibodies might block the entry of most virus genotypes and thus broadly neutralize HBV infection.

Definition of the peptide mimotope of cellular receptor for hepatitis C virus E2 protein using random peptide library (Random peptide library를 이용한 C형 간염바이러스 E2 단백질 세포막 수용체의 peptide mimotope 규명)

  • Lee, In-Hee;Paik, Jae-Eun;Seol, Sang-Yong;Seog, Dae-Hyun;Park, Sae-Gwang;Choi, In-Hak
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.77-86
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    • 2001
  • Background: Hepatitis C virus(HCV), a family of Flaviviridae, has a host cell-derived envelope containing a positive-stranded RNA genome, and has been known as the maj or etiological agent for chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. There remains a need to dissect a molecular mechanism of pathogenesis for the development of therapeutic and effective preventive measure for HCV. Identification of cellular receptor is of central importance not only to understand the viral pathogenesis, but also to exploit strategies for prevention of HCV. This study was aimed at identifying peptide mimotopes inhibiting the binding of E2 protein of HCV to MOLT-4 cell. Methods: In this study, phage peptide library displaying a random peptides consisting of 7 or 12 random peptides was employed in order to pan against E2 protein. Free HCV particles were separated from the immune complex forms by immunoprecipitation using anti-human IgG antibody, and used for HCV-capture ELISA. To identify the peptides inhibiting E2-binding to MOLT-4 cells, E2 protein was subj ect to bind to MOLT-4 cells under the competition with phage peptides. Results: Several phage peptides were selected for their specific binding to E2 protein, which showed the conserved sequence of SHFWRAP from 3 different peptide sequences. They were also able to recognize the HCV particles in the sera of HCV patients captured by monoclonal antibody against E2 protein. Two of them, showing peptide sequence of HLGPWMSHWFQR and WAPPLERSSLFY respectively, were revealed to inhibit the binding of E2 protein to MOLT-4 cell efficiently in dose dependent mode. However, few membrane-associated receptor candidates were seen using Fasta3 programe for homology search with these peptides. Conclusion: Phage peptides containing HLGPWMSHWFQR and WAPPLERSSLFY respectively, showed the inhibition of E2-binding to MOLT-4 cells. However, they did not reveal any homologues to cellular receptors from GenBank database. In further study, cellular receptor could be identified through the screening of cDNA library from MOLT-4 or hepatocytes using antibodies against these peptide mimotopes.

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First report of cross-species transmission of deer hepatitis E virus to a guanaco in Korea

  • Park, Byung-Joo;Yi, Ji-Hyung;Ahn, Hee-Seop;Han, Sang-Hoon;Kim, Yong-Hyun;Go, Hyeon-Jeong;Kim, Dong-Hwi;Lee, Joong-Bok;Park, Seung-Yong;Song, Chang-Seon;Lee, Sang-Won;Choi, In-Soo
    • Journal of Preventive Veterinary Medicine
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    • v.41 no.3
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    • pp.121-123
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    • 2017
  • The hepatitis E virus (HEV) is a leading causative agent of acute hepatitis in humans. Zoonotic HEV strains have been isolated from several animal species, including pigs. New HEV variants have been recently isolated from camels in the Middle East. In the present study, fecal samples from fallow deer, formosan deer, alpaca, and guanaco were analyzed for the detection of HEV. One HEV strain was detected from guanaco, a species of camelids. The nucleotide sequence of guanaco HEV was identical to those of deer HEV-3 strains, which implied the cross-species transmission of HEV-3 from deer to guanaco.

Hepatitis E Virus Inhibits Activation of Signaling Molecules Involved in Induction of Type I Interferon (E형 간염 바이러스에 의한 제 1형 인터페론 신호전달분자 활성 억제)

  • Myoung, Jinjong
    • Microbiology and Biotechnology Letters
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    • v.46 no.4
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    • pp.320-325
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    • 2018
  • Hepatitis E virus (HEV) infection accounts for 20 million annual infections worldwide. HEV can be fatal in approximately 20-30% of pregnant women. HEV infections are normally self-limiting and mostly asymptomatic. However, in patients with insufficient immunity, such as acquired immunodeficiency syndrome patients, chronic and often fatal infections may ensue. Therefore, it is likely that host immune responses, especially interferon responses, play a critical role in HEV infection control. Here, we report that an HEV-encoded non-structural protein down-regulates type I interferon response. In addition, some other immune genes involved in the induction of type I interferon may be regulated as well. Detailed molecular mechanisms are currently being studied.

Overexpression of the $E1_{192-283}$ and $E2_{384-649}$ Proteins of Hepatitis C Virus in GST Fusion Forms in E. coli and Their Immunogenicity (C 형 간염 바이러스의 외피당단백질 E1 및 E2의 융합단백질 $GST-E1_{192-283}$$-E2_{384-649}$의 대장균에서의 과량발현 및 면역원성 연구)

  • Seong, Young-Rim;Choi, See-Young;Im, Dong-Soo
    • The Journal of Korean Society of Virology
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    • v.27 no.2
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    • pp.105-113
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    • 1997
  • The truncated $E1_{192-283}$ and $E2_{384-649}$ genes of hepatitis C virus (HCV) linked to the gene for glutathione S-transferase (GST) were constructed and their expressions were analyzed. The $GST-E1_{192-283}$ fusion gene overexpressed the fusion protein in E. coli as a soluble form, while the $GST-E1_{192-383}$ plasmid did not express expected fusion protein. The purified $GST-E1_{192-283}$ fusion protein was efficiently cleaved by thrombin. More than 90% pure, HCV $E1_{192-283}$ protein was obtained by GST-agarose chromatography. The truncated $GST-E2_{384-649}$ fusion gene expressed the fusion protein mainly as an insoluble form, whereas the $GST-E2_{384-740}$ did not express the fusion protein. The truncated $GST-E1_{182-283}$ and $GST-E2_{384-649}$ fusion proteins reacted specifically with an HCV patient serum. In addition, mice immunized with either the purified $E1_{192-283}$ or $GST-E2_{384-649}$ proteins generated specific antibodies to each antigen. The results suggested that hydrophobic carboxyl portions of the E1 and E2 proteins might affect expression levels as well as the solubility of each fusion protein in bacteria. Also, the truncated E1 protein with Tyr-192 to Ser-283 contained antigenic epitope(s) which could be specifically recognized by an HCV patient serum.

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Array-based Nano-amplification Technique Was Applied in Detection of Hepatitis E Virus

  • Liu, Hui-Hui;Cao, Xuan;Yang, Yong;Liu, Ming-Gui;Wang, Ye-Fu
    • BMB Reports
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    • v.39 no.3
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    • pp.247-252
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    • 2006
  • A rapid method for the detection of Hepatitis E Virus (HEV) was developed by utilizing nano-gold labeled oligonucleotide probes, silver stain enhancement and the microarray technique. The 5'-end -$NH_2$ modified oligonucleotide probes were immobilized on the surface of the chip base as the capture probe. The detection probe was made of the 3'-end -SH modified oligonucleotide probe and nano-gold colloid. The optimal concentrations of these two probes were determined. To test the detection sensitivity and specificity of this technique, a conservative fragment of the virus RNA was amplified by the RT-PCR/PCR one step amplification. The cDNA was hybridized with the capture probes and the detection probes on microarray. The detection signal was amplified by silver stain enhancement and could be identified by naked eyes. 100 fM of amplicon could be detected out on the microarray. As the results, preparation of nano-gold was improved and faster. Development time also was shortened to 2 min. Thus, considering high efficiency, low cost, good specificity and high sensitivity, this technique is alternative for the detection of HEV.

Changing Patterns of Communicable Diseases in Korea (우리나라 전염성 질환의 변화 양상)

  • Lim, Hyun-Sul
    • Journal of Preventive Medicine and Public Health
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    • v.38 no.2
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    • pp.117-124
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    • 2005
  • Before twentieth centuries and during early twentieth centuries, communicable diseases were the major cause of morbidity and mortality in Korea. But reliable data are not available. After 1975, the overall morbidity and mortality from communicable diseases, rapidly declined. Recently many new pathogenic microbes were recognized: L. monocytogenes, Hantaan virus, Y. pseudotuberculosis, P. multocida, L. pneumophilia, Human immunodeficiency virus (HIV), G. seoi, H. capsulatum, C. burnetii, V. cholerae O139, C. parvum, F. tularensis, E. coli O157:H7, B. burgdorferi, S. Typhimurium DT104, Rotavirus, hepatitis C virus and so on. Since the first HIV infection recognized in 1985, the reported cases of infection and deaths from HIV/AIDS have been steady increased each year. Legionnaire's disease, E. coli O157:H7 colitis, listeriosis and crytosporidiasis have been occurring just sporadically among immunocompromized cases. Many re-emerging communicable diseases were occurred in Korea: leptospirosis, malaria, endemic typhus, cholera, tsutsugamushi disease, salmonellosis, hepatitis A, shigellosis, mumps, measles, acute hemorrhagic conjunctivitis, brucellosis and so on. Leptospirosis and tsutsugamushi diseases have been noticed as major public health problems since 1980s. The malaria that had been virtually disappeared for a decade has reappeared from 1993 with striking increase of patients in recent 3-4 years. The distributions of salmonella and shigella serotypes have been changed a lot in recent few decades. Furthermore rapid emergence of antibiotic-resistant bacterial strains induces more difficult and complex problems in control of communicable diseases. We must recognize on the importance of environment and ecosystem conservation and careful prescription of anti-microbial agent in order to prevent communicable diseases.