Genetic variability of hepatitis A virus in South America reveals heterogeneity and co-circulation during epidemic outbreaks

Costa-Mattioli, Mauro; Ferré, Virginie; Monpoeho, S.; García, Laura E.; Colina, Rodney; Billaudel, S.; Vega, I; Perez-Bercoff, R.; Cristina, Juan

doi:10.1099/0022-1317-82-11-2647

Cited by 53 publications

(42 citation statements)

References 20 publications

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“…Even in extended common-source outbreaks, viruses isolated from the first cases are genetically the same as those isolated from the last cases (63,112,170,175). However, enough genetic heterogeneity exists in several HAV genome regions to differentiate the relatedness of isolates circulating within and between communities over time, including within subgenotypes (50,51,52,161,170).…”

Section: Methods Of Molecular Epidemiologymentioning

confidence: 99%

Diagnosis of Hepatitis A Virus Infection: a Molecular Approach

et al. 2006

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SUMMARY Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and characterize nucleic acid markers of viral infections have provided the foundation for the field of molecular epidemiology and increased our knowledge of the molecular biology and epidemiology of HAV. Although HAV is primarily shed in feces, there is a strong viremic phase during infection which has allowed easy access to virus isolates and the use of molecular markers to determine their genetic relatedness. Molecular epidemiologic studies have provided new information on the types and extent of HAV infection and transmission in the United States. In addition, these new diagnostic methods have provided tools for the rapid detection of food-borne HAV transmission and identification of the potential source of the food contamination.

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Section: Methods Of Molecular Epidemiologymentioning

confidence: 99%

Diagnosis of Hepatitis A Virus Infection: a Molecular Approach

et al. 2006

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“…However, despite this limited amino acid heterogeneity, a significant degree of nucleic acid variability has been observed among different isolates from different regions of the world (3,8,23,25). The molecular bases of this genetic variability may be the high error rate of the viral RNA-dependent RNA polymerase and the absence of proofreading mechanisms.…”

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confidence: 99%

Genome Variability and Capsid Structural Constraints of Hepatitis A Virus

Sánchez

Bosch

Pintó

2003

J Virol

127

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The number of synonymous mutations per synonymous site (K s ), the number of nonsynonymous mutations per nonsynonymous site (K a ), and the codon usage statistic (N c ) were calculated for several hepatitis A virus (HAV) isolates. While K s was similar to those of poliovirus (PV) and foot-and-mouth disease virus (FMDV), K a was 1 order of magnitude lower. The N c parameter provides information on codon usage bias and decreases when bias increases. The N c 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 ␤ barrels and ␣ 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.The high degree of conservation of the amino acid sequences of the capsid proteins of hepatitis A virus (HAV) correlates with a lack of antigenic diversity; thus, there is only a single serotype of human HAV. However, despite this limited amino acid heterogeneity, a significant degree of nucleic acid variability has been observed among different isolates from different regions of the world (3,8,23,25). The molecular bases of this genetic variability may be the high error rate of the viral RNA-dependent RNA polymerase and the absence of proofreading mechanisms. Although no data exist on the error rate of the HAV polymerase, the mutation frequencies for a variety of different RNA viruses range from 10 Ϫ4 to 10 Ϫ5 substitution per base per round of copying (9). The reason why this nucleic acid heterogeneity does not correspond to amino acid heterogeneity should rely on the lack of nonsynonymous mutations, possibly due to their elimination by negative selection. However, the actual mode of transmission of very small HAV populations, frequently associated with contaminated foods, may lead to the accumulation of debilitating mutations (7). In this context, the strikingly low level of amino acid changes in the capsid region suggests strong structural constraints.In the present work, we undertook an analysis of the nucleotide and amino acid changes in sequences representing the available strains from GenBank and isolates from a food-borne hepatitis A outbreak. Since HAV structural data exist only for the 3C protein (4), structural models for the VP2, VP3, VP1, and 3D proteins have been deduced from actual data for the structural prot...

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“…On the basis of the genetic variability observed within the putative VP1/2A junction, seven HAV genotypes have been identified (49). However, an extensive study of South American HAV strains revealed that the VP1 amino terminus contains moreinformative variable positions than the VP1/2A junction (12).…”

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confidence: 99%

“…Genetic variants of HAV have been identified by sequencing of selected genome regions, including the VP3 C terminus (24), the VP1 amino terminus (2,3,7,12,14,16,47,50), and the VP1/2A junction (5,7,8,12,15,17,24,39,41,47,49,56).…”

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confidence: 99%