scholarly journals Molecular Evolution of Hepatitis A Virus: a New Classification Based on the Complete VP1 Protein

2002 ◽  
Vol 76 (18) ◽  
pp. 9516-9525 ◽  
Author(s):  
Mauro Costa-Mattioli ◽  
Juan Cristina ◽  
Héctor Romero ◽  
Raoul Perez-Bercof ◽  
Didier Casane ◽  
...  

ABSTRACT Hepatitis A virus (HAV) is a positive-stranded RNA virus in the genus Hepatovirus in the family Picornaviridae. So far, analysis of the genetic variability of HAV has been based on two discrete regions, the VP1/2A junction and the VP1 N terminus. In this report, we determined the nucleotide and deduced amino acid sequences of the complete VP1 gene of 81 strains from France, Kosovo, Mexico, Argentina, Chile, and Uruguay and compared them with the sequences of seven strains of HAV isolated elsewhere. Overall strain variation in the complete VP1 gene was found to be as high as 23.7% at the nucleotide level and 10.5% at the amino acid level. Different phylogenetic methods revealed that HAV sequences form five distinct and well-supported genetic lineages. Within these lineages, HAV sequences clustered by geographical origin only for European strains. The analysis of the complete VP1 gene allowed insight into the mode of evolution of HAV and revealed the emergence of a novel variant with a 15-amino-acid deletion located on the VP1 region where neutralization escape mutations were found. This could be the first antigenic variant of HAV so far identified.

1990 ◽  
Vol 161 (1) ◽  
pp. 7-13 ◽  
Author(s):  
S. M. Lemon ◽  
L. N. Binn ◽  
R. Marchwicki ◽  
P. C. Murphy ◽  
L.-H. Ping ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ah-Ra Lee ◽  
Sung-Geun Lee ◽  
Lae-Hyung Kang ◽  
Weon-Hwa Jheong ◽  
Soon-Young Paik

Hepatitis A virus is known to cause acute hepatitis and has significant implications for public health throughout the world. In the Republic of Korea, the number of patients with hepatitis A virus infection has been increasing rapidly since 2006. In this study, the Kor-HAV-F strain was identified as subgenotype IIIA by RT-PCR, and its identity was confirmed by nucleotide sequencing and alignment analysis. Moreover, detailed phylogenetic analysis indicated that the Kor-HAV-F strain clustered into subgenotype IIIA, including strains isolated in Japan, Norway, and India. The entire amino acid sequence of the VP1 and 2A regions was compared with that of the reference strains isolated in various countries. We found 2 amino acid changes (T168A and L96P, resp.) in the VP1 and 2A regions, which had not been found in any other hepatitis A virus strain. To our knowledge, this study is the first to report the full-length sequence of a hepatitis A virus isolated in the Republic of Korea.


mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Marli Vlok ◽  
Andrew S. Lang ◽  
Curtis A. Suttle

ABSTRACTRNA viruses, particularly genetically diverse members of thePicornavirales, are widespread and abundant in the ocean. Gene surveys suggest that there are spatial and temporal patterns in the composition of RNA virus assemblages, but data on their diversity and genetic variability in different oceanographic settings are limited. Here, we show that specific RNA virus genomes have widespread geographic distributions and that the dominant genotypes are under purifying selection. Genomes from three previously unknown picorna-like viruses (BC-1, -2, and -3) assembled from a coastal site in British Columbia, Canada, as well as marine RNA viruses JP-A, JP-B, andHeterosigma akashiwoRNA virus exhibited different biogeographical patterns. Thus, biotic factors such as host specificity and viral life cycle, and not just abiotic processes such as dispersal, affect marine RNA virus distribution. Sequence differences relative to reference genomes imply that virus quasispecies are under purifying selection, with synonymous single-nucleotide variations dominating in genomes from geographically distinct regions resulting in conservation of amino acid sequences. Conversely, sequences from coastal South Africa that mapped to marine RNA virus JP-A exhibited more nonsynonymous mutations, probably representing amino acid changes that accumulated over a longer separation. This biogeographical analysis of marine RNA viruses demonstrates that purifying selection is occurring across oceanographic provinces. These data add to the spectrum of known marine RNA virus genomes, show the importance of dispersal and purifying selection for these viruses, and indicate that closely related RNA viruses are pathogens of eukaryotic microbes across oceans.IMPORTANCEVery little is known about aquatic RNA virus populations and genome evolution. This is the first study that analyzes marine environmental RNA viral assemblages in an evolutionary and broad geographical context. This study contributes the largest marine RNA virus metagenomic data set to date, substantially increasing the sequencing space for RNA viruses and also providing a baseline for comparisons of marine RNA virus diversity. The new viruses discovered in this study are representative of the most abundant family of marine RNA viruses, theMarnaviridae, and expand our view of the diversity of this important group. Overall, our data and analyses provide a foundation for interpreting marine RNA virus diversity and evolution.


1996 ◽  
Vol 315 (3) ◽  
pp. 807-814 ◽  
Author(s):  
Said MODARESSI ◽  
Bruno CHRIST ◽  
Jutta BRATKE ◽  
Stefan ZAHN ◽  
Tilman HEISE ◽  
...  

In human liver, phosphoenolpyruvate carboxykinase (PCK; EC 4.1.1.32) is about equally distributed between cytosol and mitochondria in contrast with rat liver in which it is essentially a cytosolic enzyme. Recently, the isolation of the gene and cDNA of the human cytosolic enzyme has been reported [Ting, Burgess, Chamberlain, Keith, Falls and Meisler (1993) Genomics 16, 698–706; Stoffel, Xiang, Espinosa, Cox, Le Beau and Bell (1993) Hum. Mol. Genet. 2, 1–4]. It was the goal of this investigation to isolate the cDNA of the human mitochondrial form of hepatic PCK. A human liver cDNA library was screened with a rat cytosolic PCK cDNA probe comprising sequences from exons 2 to 9. A cDNA clone was isolated which had overall a 68% DNA sequence and a 70% deduced amino acid sequence identity with the human cytosolic PCK cDNA. Without the flanking 270 bases (=90 amino acids) each at the 5´ and 3´ end, the sequence identity was 73% on the DNA and 78% on the amino acid level. The isolated cDNA had an open reading frame of 1920 bp; it was 54 bp (equivalent to 18 amino acids) longer than that of human or rat cytosolic PCK cDNA. The isolated cDNA was cloned into the eukaryotic expression vector pcDNAI and transfected into human embryonal kidney cells HEK293; PCK activity was increased by 3-fold in the mitochondria, which normally contain 70% of total PCK activity, but not in the cytosol. The isolated cDNA was also transfected into cultured rat hepatocytes; again, PCK activity was enhanced by about 40-fold in the mitochondria, which normally possess only 10% of total PCK activity, but not in the cytosol. In the rat hepatocytes only the endogenous cytosolic PCK and not the transfected mitochondrial PCK was induced 3-fold with glucagon. Comparison of the amino acid sequences deduced from the isolated cDNA with human and rat cytosolic PCK showed that the additional 18 amino acids were located at the N-terminus of the protein and probably constitute a mitochondrial targeting signal. Northern-blot analyses revealed the human mitochondrial PCK mRNA to be 2.25 kb long, about 0.6 kb shorter than the mRNA of the cytosolic PCK. Primer extension experiments showed that the 5´-untranslated region of mitochondrial PCK mRNA was 134 nucleotides in length.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3391 ◽  
Author(s):  
Dariya K. Sydykova ◽  
Claus O. Wilke

Site-specific evolutionary rates can be estimated from codon sequences or from amino-acid sequences. For codon sequences, the most popular methods use some variation of the dN∕dS ratio. For amino-acid sequences, one widely-used method is called Rate4Site, and it assigns a relative conservation score to each site in an alignment. How site-wise dN∕dS values relate to Rate4Site scores is not known. Here we elucidate the relationship between these two rate measurements. We simulate sequences with known dN∕dS, using either dN∕dS models or mutation–selection models for simulation. We then infer Rate4Site scores on the simulated alignments, and we compare those scores to either true or inferred dN∕dS values on the same alignments. We find that Rate4Site scores generally correlate well with true dN∕dS, and the correlation strengths increase in alignments with greater sequence divergence and more taxa. Moreover, Rate4Site scores correlate very well with inferred (as opposed to true) dN∕dS values, even for small alignments with little divergence. Finally, we verify this relationship between Rate4Site and dN∕dS in a variety of empirical datasets. We conclude that codon-level and amino-acid-level analysis frameworks are directly comparable and yield very similar inferences.


Praxis ◽  
2003 ◽  
Vol 92 (40) ◽  
pp. 1659-1673 ◽  
Author(s):  
Siegl

Die Hepatitis A wird durch das Hepatitis A-Virus verursacht, ein kleines, ausgesprochen umweltresistentes RNA-Virus, das als Schmutz- und Schmierinfektion übertragen wird, und sich offensichtlich ausschliesslich in der Leber vermehrt. Die dabei ausgelöste Schädigung der Leber ist wahrscheinlich auf eine zellvermittelte Immunreaktion zurückzuführen. Die Infektion ist selbstlimitierend, kann in Einzelfällen zwar lange andauern, wird aber nie chronisch. Das Virus ist weltweit verbreitet und infiziert in Ländern mit schlechten sanitären Verhältnissen praktisch 100% der Bevölkerung im Kindesalter. In diesem Alter verläuft die Infektion weitgehend symptomlos, die Infizierten entwickeln dabei aber eine lebenslang anhaltende Immunität. In der Schweiz und anderen Ländern der industrialisierten Welt ist das HAV aus der Zirkulation in der Bevölkerung weitgehend verschwunden. Infektionen treten meist erst im Erwachsenenalter auf, nach Reisen in Endemiegebiete oder nach direktem Kontakt mit infizierten Personen. Sie verlaufen mit zunehmendem Alter vermehrt apparent und schwer, in Einzelfällen sogar fulminant und tödlich. Zum Schutz vor der Hepatitis A gibt es seit rund zehn Jahren eine gutverträgliche Impfung, die einen mindestens 20 Jahre, wahrscheinlich aber sogar lebenslänglich anhaltenden Immunschutz auslöst.


1996 ◽  
Vol 8 (4) ◽  
pp. 789 ◽  
Author(s):  
PJ Greenwood ◽  
C Seamer ◽  
DJ Tisdall

By means of reverse transcription polymerase chain reaction (RT-PCR), three stem cell factor (SCF) cDNAs (822-738 bp in size) were amplified from brushtail possum ovarian poly (A)+ RNA. The largest and smallest of these cDNAs were cloned and sequenced. Characterization of these cDNAs has revealed that possum SCF has approximately 75% and 66% homology to SCF of eutherian mammals at the nucleotide level and the predicted amino acid level respectively. Nucleotide sequencing shows that the 738-bp cDNA represents an mRNA splice variant, equivalent to that found in eutherian mammals, in which an exon (84 bp) encoding a potential proteolytic cleavage site is removed. Comparison of the predicted possum SCF amino acid sequence with the predicted SCF amino acid sequences from eutherian mammals reveals conservation of all cysteine residues and 3 of 4 potential N-linked glycosylation sites. In addition, the hydropathicity profile of the possum SCF protein is similar to that of eutherian SCF suggesting that protein conformation is conserved. Northern analysis was used to characterize possum SCF gene expression in adult ovary and testis. A major transcript of 9 kb was observed in both ovarian and testicular tissue. The conservation of the SCF gene and its predicted protein, suggests that SCF in the possum has similar biological activities to SCF in eutherian mammals.


2021 ◽  
Author(s):  
Khrystyna Hrynkevych ◽  
Heinz-Josef Schmitt

Hepatitis A virus (HAV) is a single-stranded “nonenveloped” RNA virus in the picornaviridae family. HAV is most often transmitted by the fecal-oral route, but also by contaminated food, water, sexual contact, and intravenous drug use. HAV causes little if any symptoms in the very young. Disease symptoms from liver damage become more frequent in older ages and even fulminant liver failure with death is observed in the elderly. Unlike hepatitis B and C, hepatitis A does not cause chronic liver disease. With lack of sanitation and hygiene, HAV infection occurs early in life inducing life-long protection, whereas in countries with good sanitation and hygiene, infections are seen later in life and are more severe. There is no causal treatment, but available vaccines are well tolerated, have an excellent safety profile and are highly effective with long-lasting protection after 2 doses. Hepatitis A vaccines can be used for pre- as well as for post-exposure prophylaxis and for individual as well as for population protection. Vaccinating a small fraction of the population (3%) – i.e., children aged 1–4 years serving as the reservoir and source of HAV – resulted in herd protection with 96% disease reduction in the whole population of Israel.


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