scholarly journals Hepatitis A Virus Mutant Spectra under the Selective Pressure of Monoclonal Antibodies: Codon Usage Constraints Limit Capsid Variability

2007 ◽  
Vol 82 (4) ◽  
pp. 1688-1700 ◽  
Author(s):  
Lluís Aragonès ◽  
Albert Bosch ◽  
Rosa M. Pintó
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis A ◽  
Evolutionary Dynamics ◽  
Hepatitis A Virus ◽  
Structural Constraints ◽  
Immune Pressure ◽  
Virus Mutant ◽  
Dominant Mutants ◽  
Selection Of

ABSTRACT Severe structural constraints in the hepatitis A virus (HAV) capsid have been suggested as the reason for the lack of emergence of new serotypes in spite of the occurrence of complex distributions of mutants or quasispecies. Analysis of the HAV mutant spectra under immune pressure by the monoclonal antibodies (MAbs) K34C8 (immunodominant site) and H7C27 (glycophorin binding site) has revealed different evolutionary dynamics. Populations composed of complex ensembles of mutants with very low fitness or single dominant mutants with high fitness permit the acquisition of resistance to each of the MAbs, respectively. Deletion mutants were detected as components of the mutant spectra: up to 61 residues, with an average of 19, and up to 83 residues, with an average of 45, in VP3 and VP1 proteins, respectively. A clear negative selection of those replacements affecting the residues encoded by rare codons of the capsid surface has been detected through the present quasispecies analysis, confirming a certain beneficial role of such clusters. Since these clusters are located near or at the epitope regions, the need to maintain such clusters might prevent the emergence of new serotypes.

scholarly journals Evidence for positive selection of hepatitis A virus antigenic variants in vaccinated men-having-sex-with men patients: Implications for immunization policies

EBioMedicine ◽  
2019 ◽  
Vol 39 ◽  
pp. 348-357 ◽  
Author(s):  
Aurora Sabrià ◽  
Josep Gregori ◽  
Damir Garcia-Cehic ◽  
Susana Guix ◽  
Tomàs Pumarola ◽  
...  
Keyword(s):  
Positive Selection ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Sex With Men ◽  
Selection Of

scholarly journals Duck Hepatitis A Virus Type 1 Induces eIF2α Phosphorylation-Dependent Cellular Translation Shutoff via PERK/GCN2

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanzhi Liu ◽  
Anchun Cheng ◽  
Mingshu Wang ◽  
Sai Mao ◽  
Xumin Ou ◽  
...  
Keyword(s):  
Virus Type ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Translation Efficiency ◽  
Eif2α Phosphorylation ◽  
Duck Hepatitis ◽  
Cellular Translation ◽  
First Time

Duck hepatitis A virus type 1 (DHAV-1) is one of the most deadly pathogens that endanger the duck industry. Most viruses usually turn off host translation after infection to facilitate viral replication and translation. For the first time report to our knowledge, DHAV-1 can induce eIF2α phosphorylation and inhibit cellular translation in duck embryo fibroblasts (DEFs). Moreover, the activity of DHAV-1 in the cells caused obvious eIF2α phosphorylation, which has nothing to do with the viral protein. Subsequently, we screened two kinases (PERK and GCN2) that affect eIF2α phosphorylation through inhibitors and shRNA. Notably, the role of GCN2 in other picornaviruses has not been reported. In addition, when the phosphorylation of eIF2α induced by DHAV-1 is inhibited, the translation efficiency of DEFs restores to a normal level, indicating that DHAV-1 induced cellular translation shutoff is dependent on eIF2α phosphorylation.

Negative Serology for Hepatitis A and B Viruses in 18 Cases of Neonatal Cholestasis

PEDIATRICS ◽  
1980 ◽  
Vol 66 (2) ◽  
pp. 269-271
Author(s):  
William F. Balistreri ◽  
Edward Tabor ◽  
Robert J. Gerety
Keyword(s):  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Maternal Serum ◽  
Hbv Infection ◽  
Core Antigen ◽  
Neonatal Cholestasis ◽  
Immune Adherence ◽  
B Virus ◽  
Serologic Evidence

Serologic evidence of hepatitis A virus (HAV) or hepatitis B virus (HBV) infection was sought in 14 patients with biliary atresia and in four patients with neonatal hepatitis; maternal serum was also analyzed. Specific sensitive radioimmunoassays were used to detect HBV surface antigen (HBsAg) and antibody (anti-HBs); complement fixation was used to detect antibody to HBV core antigen (anti-HBc). Antibody to HAV (anti-HAV) was assayed by radioimmunoassay, as well as by immune adherence hemagglutination. There was no evidence of active or past HBV infection in any infant or mother studied. All three infants with detectable anti-HAV were born to mothers similarly anti-HAV positive; serial testing of sera from two of these infants documented disappearance of detectable anti-HAV by 9 months of age. It is unlikely, therefore, that either HAV or HBV had an etiologic role in neonatal cholestasis in these patients. The role of other (non-A, non-B) hepatitis viruses or nonviral etiologies must be investigated.

scholarly journals The Critical Role of Codon Composition on the Translation Efficiency Robustness of the Hepatitis A Virus Capsid

2019 ◽  
Vol 11 (9) ◽  
pp. 2439-2456 ◽  
Author(s):  
Lucía D’Andrea ◽  
Francisco-Javier Pérez-Rodríguez ◽  
Montserrat de Castellarnau ◽  
Susana Guix ◽  
Enric Ribes ◽  
...  
Keyword(s):  
Codon Usage ◽  
Sequence Space ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Critical Role ◽  
Translation Efficiency ◽  
Rare Codons ◽  
Codon Composition ◽  
Cellular Genome

AbstractHepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype–phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype–phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff—not naturally occurring in HAV infection—involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.

scholarly journals Four Chimpanzee Monoclonal Antibodies Isolated by Phage Display Neutralize Hepatitis A Virus

Virology ◽  
2002 ◽  
Vol 292 (1) ◽  
pp. 127-136 ◽  
Author(s):  
D.J. Schofield ◽  
W. Satterfield ◽  
S.U. Emerson ◽  
R.H. Purcell
Keyword(s):  
Monoclonal Antibodies ◽  
Phage Display ◽  
Hepatitis A ◽  
Hepatitis A Virus

scholarly journals Genome Variability and Capsid Structural Constraints of Hepatitis A Virus

2003 ◽  
Vol 77 (1) ◽  
pp. 452-459 ◽  
Author(s):  
Glòria Sánchez ◽  
Albert Bosch ◽  
Rosa M. Pintó
Keyword(s):  
Codon Usage ◽  
Rna Structure ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Foot And Mouth Disease ◽  
Structural Constraints ◽  
Translation Speed ◽  
Synonymous Mutations ◽  
Rare Codons ◽  
Mouth Disease Virus

ABSTRACT The number of synonymous mutations per synonymous site (Ks ), the number of nonsynonymous mutations per nonsynonymous site (Ka ), and the codon usage statistic (Nc ) were calculated for several hepatitis A virus (HAV) isolates. While Ks was similar to those of poliovirus (PV) and foot-and-mouth disease virus (FMDV), Ka was 1 order of magnitude lower. The Nc parameter provides information on codon usage bias and decreases when bias increases. The Nc value in HAV was about 38, while in PV and FMDV, it was about 53. The emergence of 22 rare codons in front of 8 in PV and 7 in FMDV was detected. Most of the conserved rare codons of the P1 region were strategically located at the carboxy borders of β barrels and α helices, their potential function being the assurance of proper folding of the capsid proteins through a decrease in the translation speed. This strategic location was not observed for amino acids encoded by the conserved rare codons of the 3D region. The percentage of bases with low pairing number values was higher in the latter region, suggesting a role of the conserved rare codons in the maintenance of RNA structure. Many of the rare codons in HAV are among the most frequent in humans, unlike in PV or in FMDV. This fact may be explained by the lack of cellular shutoff in HAV. One hypothesis is that HAV has evolved in order to avoid competition with its host for cellular tRNAs.

scholarly journals RECENT CHANGES OF HEPATITIS A EPIDEMIOLOGY IN RUSSIA AND EUROPE AS THE RATIONALES FOR PREVENTION STRATEGIES

2012 ◽  
Vol 17 (3) ◽  
pp. 28-34
Author(s):  
V. P. Chulanov ◽  
N. N. Pimenov ◽  
I. V. Karandashova ◽  
S. V. Komarova
Keyword(s):  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Molecular Genetic ◽  
Critical Role ◽  
Herd Immunity ◽  
Age Groups ◽  
Control Measures ◽  
Prevention Strategies ◽  
Molecular Genetic Diversity

The article describes results of the analysis of incidence rate of hepatitis A in Russia and 29 European countries over the period 2001 to 2008. The characteristic of hepatitis A outbreaks as well as molecular genetic diversity of hepatitis A virus in Russia and Europe has been compared. The authors analyze the state of herd immunity to hepatitis A virus in population of the territories of countries mentioned above. The results of seroprevalence study of hepatitis A virus among different age groups in Moscow are presented. The critical role of hepatitis A vaccination in the system of prevention and disease control measures is emphasized.

scholarly journals Effect of Cholesterol on Membrane Partitioning Dynamics of Hepatitis A Virus-2B peptide

Soft Matter ◽  
2021 ◽  
Author(s):  
Samapan Sikdar ◽  
Manidipa Banerjee ◽  
Satyavani Vemparala
Keyword(s):  
Crucial Role ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Membrane Composition ◽  
Viral Peptide ◽  
Membrane Partitioning ◽  
Peptide Detection ◽  
Host Membrane

Understanding the viral peptide detection, partitioning and subsequent host membrane composition-based response is required for gaining insights into viral mechanism. Here, we probe the crucial role of presence of membrane...

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