Genetic point mutation inducing antigenic drift in hypervariable region of avery virulant IBDV isolate in chickens in Egypt during 2014-2016

Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses

Journal of Virology ◽

10.1128/jvi.02995-15 ◽

2015 ◽

Vol 90 (7) ◽

pp. 3318-3329 ◽

Cited By ~ 5

Author(s):

Brendan A. Palmer ◽

Daniel Schmidt-Martin ◽

Zoya Dimitrova ◽

Pavel Skums ◽

Orla Crosbie ◽

...

Keyword(s):

Hepatitis C ◽

Amino Acid ◽

Chronic Infection ◽

Hypervariable Region ◽

Antigenic Drift ◽

Single Amino Acid ◽

Connected Components ◽

Adaptive Mutations ◽

Humoral Immune ◽

Hypervariable Region 1

ABSTRACTHypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space.IMPORTANCEHCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness.

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Hypervariable region 1 quasispecies in chronic hepatitis C patients: influence of genotype

Journal of Hepatology ◽

10.1016/s0168-8278(01)80397-4 ◽

2001 ◽

Vol 34 (0) ◽

pp. 110

Author(s):

T Asselah

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Hypervariable Region ◽

Hypervariable Region 1 ◽

Chronic Hepatitis C Patients

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Paris I Dysfibrinogenemia: A Point Mutation in Intron 8 Results in Insertion of a 15 Amino Acid Sequence in the Fibrinogen γ-Chain

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651583 ◽

1993 ◽

Vol 69 (03) ◽

pp. 217-220 ◽

Cited By ~ 12

Author(s):

Jonathan B Rosenberg ◽

Peter J Newman ◽

Michael W Mosesson ◽

Marie-Claude Guillin ◽

David L Amrani

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Point Mutation ◽

Genomic Dna ◽

Comparative Sequence Analysis ◽

Chain Gene ◽

Molecular Defect ◽

Nucleotide Position ◽

Normal Individuals ◽

Polymerase Chain

SummaryParis I dysfibrinogenemia results in the production of a fibrinogen molecule containing a functionally abnormal γ-chain. We determined the basis of the molecular defect using polymerase chain reaction (PCR) to amplify the γ-chain region of the Paris I subject’s genomic DNA. Comparative sequence analysis of cloned PCR segments of normal and Paris I genomic DNA revealed only an A→G point mutation occurring at nucleotide position 6588 within intron 8 of the Paris I γ-chain gene. We examined six normal individuals and found only normal sequence in this region, indicating that this change is not likely to represent a normal polymorphism. This nucleotide change leads to a 45 bp fragment being inserted between exons 8 and 9 in the mature γparis I chain mRNA, and encodes a 15 amino acid insert after γ350 [M-C-G-E-A-L-P-M-L-K-D-P-C-Y]. Alternative splicing of this region from intron 8 into the mature Paris I γ-chain mRNA also results after translation into a substitution of S for G at position γ351. Biochemical studies of 14C-iodoacetamide incorporation into disulfide-reduced Paris I and normal fibrinogen corroborated the molecular biologic predictions that two additional cysteine residues exist within the γpariS I chain. We conclude that the insertion of this amino acid sequence leads to a conformationallyaltered, and dysfunctional γ-chain in Paris I fibrinogen.

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