HBV mutations and their clinical significance

Łapiński, Tadeusz Wojciech; Pogorzelska, Joanna; Flisiak, Robert

doi:10.2478/v10039-012-0006-x

Cited by 18 publications

(10 citation statements)

References 17 publications

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“…The sequences were finally aligned with two wild type HBV genotype D sequence from China and India, obtained from GenBank (accession numbers FJ899792 and AY161159) to detect amino acid substitutions. The sequences were also analyzed for HBV resistance drugs [3][4][5] . Since the HBV genome does not have a proofreading ability, the mutations occur with a very high frequency of occurrence [6] .…”

Section: Analysis Of the Sequencesmentioning

confidence: 99%

Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Mahmood¹,

Anwar²

2017

JUMD

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Aim:To explore nucleoside/nucleotide analogues resistance mutations in hepatitis B virus (HBV) reverse transcriptase (RT) domain from non-responder Pakistani patients. Methods: Blood samples were taken from 20 chronic HBV patients who were non-responders to different nucleoside/nucleotide analogues. HBV DNA was extracted and a fragment of genome including RT domain was sequenced. The sequence was aligned with wild type HBV sequences and compared with resistant mutations in the RT domain. Results: Resistant mutations were detected in samples of 13 (65%) patients who were non-responders to more than one drug. The mutations were found at amino acid positions rt80, rt135, rt169, rt173, rt180, rt181, rt184 and rt204 and rt248. Mutations rtY135S and rtN248H were detected from 13 (65%) and 12 (60%) samples respectively. Mutations rtL180M and rtA181V were present in 6 (30%) samples, rtM204V and rtV173L in 5 (25%) samples while rtI169P, rtL80G and rtT184Y were identified from 3 (15%), 2 (10%) and 1 (5%) sample respectively. Conclusion: Nucleoside /Nucleotide analogues resistant mutations rt135, rtL180M, rtA181V, rtM204V, rtV173L and rtN248H are frequent in HBV strains isolated from non-responder Pakistani patients while mutations rtI169P, rtL80G and rtT184Y are also present in low proportion. Key words:Hepatitis B virus, resistant mutations, reverse transcriptase, nucleos(t)ide analogues, Pakistan ABSTRACTArticle history:

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Section: Analysis Of the Sequencesmentioning

confidence: 99%

Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Mahmood¹,

Anwar²

2017

JUMD

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“…Despite the effectiveness of these yeastderived vaccines, HBV variants with mutations across the "a" determinant have been shown to escape the immune responses generated by the yeast-derived HBsAg (10)(11)(12)(13). In addition, vaccine escape mutants with nucleotide changes in their polymerase and HBsAg genes have been reported widely due to continuous treatment of patients with chronic hepatitis B with nucleoside analogs (14). These life-threatening mutants and the genetic diversity of the HBV genome strongly justify a continuing need for the development of new HBV vaccines (15).…”

mentioning

confidence: 99%

Induction of Humoral and Cell-Mediated Immune Responses by Hepatitis B Virus Epitope Displayed on the Virus-Like Particles of Prawn Nodavirus

Yong

Yeap

Goh

et al. 2015

Appl Environ Microbiol

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Hepatitis B virus (HBV) is a deadly pathogen that has killed countless people worldwide. Saccharomyces cerevisiae-derived HBV vaccines based upon hepatitis B surface antigen (HBsAg) is highly effective. However, the emergence of vaccine escape mutants due to mutations on the HBsAg and polymerase genes has produced a continuous need for the development of new HBV vaccines. In this study, the "a" determinant within HBsAg was displayed on the recombinant capsid protein of Macrobrachium rosenbergii nodavirus (MrNV), which can be purified easily in a single step through immobilized metal affinity chromatography (IMAC). The purified protein self-assembled into virus-like particles (VLPs) when observed under a transmission electron microscope (TEM). Immunization of BALB/c mice with this chimeric protein induced specific antibodies against the "a" determinant. In addition, it induced significantly more natural killer and cytotoxic T cells, as well as an increase in interferon gamma (IFN-␥) secretion, which are vital for virus clearance. Collectively, these findings demonstrated that the MrNV capsid protein is a potential carrier for the HBV "a" determinant, which can be further extended to display other foreign epitopes. This paper is the first to report the application of MrNV VLPs as a novel platform to display foreign epitopes. Hepatitis B virus (HBV) is a partially double-stranded DNA virus that belongs to the family Hepadnaviridae. It is known to be the major cause of liver-associated diseases, including liver cirrhosis and hepatocellular carcinoma. Approximately 2 billion people worldwide have been infected by HBV, among which about 350 million chronically infected people serve as a reservoir for the virus (1, 2). To date, there is no effective treatment for HBV infection despite intensive studies on antiviral drugs. Thus, preventive measures, including immunization with HBV vaccine, remain necessary.HBV surface antigens (HBsAg) purified from the sera of infected patients have been used for immunization against HBV infection since 1981. The full-length HBsAg gene has three different start codons and a common stop codon and encodes HBsAg of different lengths (3). The longest is the large HBsAg (L-HBsAg), followed by the middle HBsAg (M-HBsAg), and the smallest is the small HBsAg (S-HBsAg). L-HBsAg is composed of 389 or 400 amino acids (aa), depending on the virus genotypes. It contains the pre-S1 region (108 or 119 aa), followed by the pre-S2 region (55 aa) and S-HBsAg (226 aa). The N-terminal end of M-HBsAg harbors the pre-S2 region at its S-HBsAg. The S-HBsAg contains 226 aa in the absence of the pre-S1 and pre-S2 regions.The HBsAg in serum self-assemble into noninfectious 22-nm spherical or filamentous particles, along with lipid components (4), which are capable of inducing neutralizing antibodies against HBV infection. Although highly effective, the use of plasma-derived HBsAg for vaccination is limited by the production cost, as well as the possibility of contamination by other infectious pathogens present in...

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“…Members of the MMPs family are also expressed in MM microenvironment and are implicated in tumor growth and dissemination, angiogenesis and development of osteolytic lesions. In particular, MMP-9 and possibly MMP-2 are synthesized by MM cells, which also contribute to the activation of the latent forms [27], [46]. Accordingly, MMP-9 and -2 were expressed and increased over-time in supernatants; notably, the active forms were detectable during culture, indicating the existence of efficient cell-to-cell interactions.…”

Section: Discussionmentioning

confidence: 99%

Ex-Vivo Dynamic 3-D Culture of Human Tissues in the RCCS™ Bioreactor Allows the Study of Multiple Myeloma Biology and Response to Therapy

et al. 2013

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Three-dimensional (3-D) culture models are emerging as invaluable tools in tumor biology, since they reproduce tissue-specific structural features and cell-cell interactions more accurately than conventional 2-D cultures. Multiple Myeloma, which depends on myeloma cell-Bone Marrow microenvironment interactions for development and response to drugs, may particularly benefit from such an approach. An innovative 3-D dynamic culture model based on the use of the RCCS™ Bioreactor was developed to allow long-term culture of myeloma tissue explants. This model was first validated with normal and pathological explants, then applied to tissues from myeloma patients. In all cases, histological examination demonstrated maintenance of viable myeloma cells inside their native microenvironment, with an overall well preserved histo-architecture including bone lamellae and vessels. This system was then successfully applied to evaluate the cytotoxic effects exerted by the proteasome inhibitor Bortezomib not only on myeloma cells but also on angiogenic vessels. Moreover, as surrogate markers of specialized functions expressed by myeloma cells and microenvironment, β2 microglobulin, VEGF and Angiopoietin-2 levels, as well as Matrix Metalloproteases activity, were evaluated in supernatants from 3D cultures and their levels reflected the effects of Bortezomib treatment. Notably, determination of β2 microglobulin levels in supernatants from Bortezomib-treated samples and in patients'sera following Bortezomib-based therapies disclosed an overall concordance in the response to the drug ex vivo and in vivo.Our findings indicate, as a proof of principle, that 3-D, RCCS™ bioreactor-based culture of tissue explants can be exploited for studying myeloma biology and for a pre-clinical approach to patient-targeted therapy.

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HBV mutations and their clinical significance

Cited by 18 publications

References 17 publications

Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Analysis of resistant mutations in reverse transcriptase domain of hepatitis B virus from patients from Islamabad, Pakistan

Induction of Humoral and Cell-Mediated Immune Responses by Hepatitis B Virus Epitope Displayed on the Virus-Like Particles of Prawn Nodavirus

Ex-Vivo Dynamic 3-D Culture of Human Tissues in the RCCS™ Bioreactor Allows the Study of Multiple Myeloma Biology and Response to Therapy

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