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Basic Characteristics of Mutations
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Mutation Site
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F8L |
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Mutation Site Sentence
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Conversely, 2 HBsAg mutations (F8L and Y100C) significantly correlated with serum HBV-DNA >100,000 IU/ml. Both mutations occurred in 1.7% of patients with serum HBV-DNA ≤2000 IU/ml and their prevalence increased up to 13% and 10.1% in patients with serum HBV-DNA >100,000 IU/ml, respectively. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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D;A |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Hepatitis B, Chronic
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Immune
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Y |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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Italy |
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Literature Information
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PMID
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25452041
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Title
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Specific mutations in the C-terminus domain of HBV surface antigen significantly correlate with low level of serum HBV-DNA in patients with chronic HBV infection
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Author
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Mirabelli C,Surdo M,Van Hemert F,Lian Z,Salpini R,Cento V,Cortese MF,Aragri M,Pollicita M,Alteri C,Bertoli A,Berkhout B,Micheli V,Gubertini G,Santoro MM,Romano S,Visca M,Bernassola M,Longo R,De Sanctis GM,Trimoulet P,Fleury H,Marino N,Mazzotta F,Cappiello G,Spano A,Sarrecchia C,Zhang JM,Andreoni M,Angelico M,Verheyen J,Perno CF,Svicher V
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Journal
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The Journal of infection
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Journal Info
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2015 Mar;70(3):288-98
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Abstract
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BACKGROUND: To define HBsAg-mutations correlated with different serum HBV-DNA levels in HBV chronically-infected drug-naive patients. METHODS: This study included 187 patients stratified into the following ranges of serum HBV-DNA:12-2000 IU/ml, 2000-100,000 IU/ml, and >100,000 IU/ml. HBsAg-mutations were associated with HBV-DNA levels by applying a Bayesian-Partitional-Model and Fisher-exact test. Mutant and wild-type HBV genotype-D genomes were expressed in Huh7 cells and HBsAg-production was determined in cell-supernatants at 3 days-post-transfection. RESULTS: Specific HBsAg-mutations (M197T,-S204N-Y206C/H-F220L) were significantly correlated with serum HBV-DNA <2000 IU/ml (posterior-probability>90%, P < 0.05). The presence of Y206C/H and/or F220L was also associated with lower median (IQR) HBsAg-levels and lower median (IQR) transaminases (for HBsAg:250[115-840] IU/ml for Y206C/H and/or F220L versus 4300[640-11,838] IU/ml for wild-type, P = 0.023; for ALT:28[21-40] IU/ml versus 53[34-90] IU/ml, P < 0.001). These mutations were localized in the HBsAg C-terminus, known to be involved in virion and/or HBsAg secretion. The co-occurrence of Y206C + F220L was found significant by cluster-analysis, (P = 0.02). In addition, in an in-vitro model Y206C + F220L determined a 2.8-3.3 fold-reduction of HBsAg-amount released in supernatants compared to single mutants and wt (Y206C + F220L = 5,679 IU/ml; Y206H = 16,305 IU/ml; F220L = 18,368 IU/ml; Y206C = 18,680 IU/ml; wt = 14,280 IU/ml, P < 0.05). CONCLUSIONS: Specific HBsAg-mutations (compartmentalized in the HBsAg C-terminus) correlated with low-serum HBV-DNA and HBsAg-levels. These findings can be important to understand mechanisms underlying low HBV replicative potential including the inactive-carrier state.
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Sequence Data
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KF862505-KF862682
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