Pathogenicity and Virulence of Hepatitis A Virus

Overview

Journal Virulence

Specialty Microbiology

Date 2021 Apr 12

PMID 33843464

Citations 15

Authors

Rosa M Pinto

Francisco-Javier Perez-Rodriguez

Maria-Isabel Costafreda

Gemma Chavarria-Miro

Susana Guix

Enric Ribes

Albert Bosch

Affiliations

Soon will be listed here.

Abstract

Hepatitis A is an acute infection of the liver, which is mostly asymptomatic in children and increases the severity with age. Although in most patients the infection resolves completely, in a few of them it may follow a prolonged or relapsed course or even a fulminant form. The reason for these different outcomes is unknown, but it is generally accepted that host factors such as the immunological status, age and the occurrence of underlaying hepatic diseases are the main determinants of the severity. However, it cannot be ruled out that some virus traits may also contribute to the severe clinical outcomes. In this review, we will analyze which genetic determinants of the virus may determine virulence, in the context of a paradigmatic virus in terms of its genomic, molecular, replicative, and evolutionary features.

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References

Yang Y, Liang Y, Qu L, Chen Z, Yi M, Li K . Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor. Proc Natl Acad Sci U S A. 2007; 104(17):7253-8. PMC: 1855380. DOI: 10.1073/pnas.0611506104. View

Hirai-Yuki A, Hensley L, McGivern D, Gonzalez-Lopez O, Das A, Feng H . MAVS-dependent host species range and pathogenicity of human hepatitis A virus. Science. 2016; 353(6307):1541-1545. PMC: 5068972. DOI: 10.1126/science.aaf8325. View

McKnight K, Xie L, Gonzalez-Lopez O, Rivera-Serrano E, Chen X, Lemon S . Protein composition of the hepatitis A virus quasi-envelope. Proc Natl Acad Sci U S A. 2017; 114(25):6587-6592. PMC: 5488923. DOI: 10.1073/pnas.1619519114. View

Alizon S, Hurford A, Mideo N, van Baalen M . Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future. J Evol Biol. 2009; 22(2):245-59. DOI: 10.1111/j.1420-9101.2008.01658.x. View

Aragones L, Guix S, Ribes E, Bosch A, Pinto R . Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid. PLoS Pathog. 2010; 6(3):e1000797. PMC: 2832697. DOI: 10.1371/journal.ppat.1000797. View

Nelemans T, Kikkert M . Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections. Viruses. 2019; 11(10). PMC: 6832425. DOI: 10.3390/v11100961. View

Hirai-Yuki A, Hensley L, Whitmire J, Lemon S . Biliary Secretion of Quasi-Enveloped Human Hepatitis A Virus. mBio. 2016; 7(6). PMC: 5142623. DOI: 10.1128/mBio.01998-16. View

Abad F, Pinto R, Bosch A . Survival of enteric viruses on environmental fomites. Appl Environ Microbiol. 1994; 60(10):3704-10. PMC: 201876. DOI: 10.1128/aem.60.10.3704-3710.1994. View

Feng Z, Hirai-Yuki A, McKnight K, Lemon S . Naked Viruses That Aren't Always Naked: Quasi-Enveloped Agents of Acute Hepatitis. Annu Rev Virol. 2016; 1(1):539-60. DOI: 10.1146/annurev-virology-031413-085359. View

10.

Pinto R, Perez-Rodriguez F, DAndrea L, de Castellarnau M, Guix S, Bosch A . Hepatitis A Virus Codon Usage: Implications for Translation Kinetics and Capsid Folding. Cold Spring Harb Perspect Med. 2018; 8(10). PMC: 6169985. DOI: 10.1101/cshperspect.a031781. View

11.

Feng Z, Li Y, McKnight K, Hensley L, Lanford R, Walker C . Human pDCs preferentially sense enveloped hepatitis A virions. J Clin Invest. 2014; 125(1):169-76. PMC: 4382264. DOI: 10.1172/JCI77527. View

12.

Kauder S, Racaniello V . Poliovirus tropism and attenuation are determined after internal ribosome entry. J Clin Invest. 2004; 113(12):1743-53. PMC: 420511. DOI: 10.1172/JCI21323. View

13.

Stern A, Yeh M, Zinger T, Smith M, Wright C, Ling G . The Evolutionary Pathway to Virulence of an RNA Virus. Cell. 2017; 169(1):35-46.e19. PMC: 5787669. DOI: 10.1016/j.cell.2017.03.013. View

14.

Bosch A, Pinto R, Guix S . Foodborne viruses. Curr Opin Food Sci. 2020; 8:110-119. PMC: 7104227. DOI: 10.1016/j.cofs.2016.04.002. View

15.

Fujiwara K, Yokosuka O, Ehata T, Saisho H, Saotome N, Suzuki K . Association between severity of type A hepatitis and nucleotide variations in the 5' non-translated region of hepatitis A virus RNA: strains from fulminant hepatitis have fewer nucleotide substitutions. Gut. 2002; 51(1):82-8. PMC: 1773280. DOI: 10.1136/gut.51.1.82. View

16.

Feng Z, Lemon S . Peek-a-boo: membrane hijacking and the pathogenesis of viral hepatitis. Trends Microbiol. 2013; 22(2):59-64. PMC: 3918648. DOI: 10.1016/j.tim.2013.10.005. View

17.

Mackiewicz V, Cammas A, Desbois D, Marchadier E, Pierredon S, Beaulieux F . Nucleotide variability and translation efficiency of the 5' untranslated region of hepatitis A virus: update from clinical isolates associated with mild and severe hepatitis. J Virol. 2010; 84(19):10139-47. PMC: 2937785. DOI: 10.1128/JVI.02598-09. View

18.

Jiang W, Ma P, Deng L, Liu Z, Wang X, Liu X . Hepatitis A virus structural protein pX interacts with ALIX and promotes the secretion of virions and foreign proteins through exosome-like vesicles. J Extracell Vesicles. 2020; 9(1):1716513. PMC: 7006762. DOI: 10.1080/20013078.2020.1716513. View

19.

Qu L, Feng Z, Yamane D, Liang Y, Lanford R, Li K . Disruption of TLR3 signaling due to cleavage of TRIF by the hepatitis A virus protease-polymerase processing intermediate, 3CD. PLoS Pathog. 2011; 7(9):e1002169. PMC: 3169542. DOI: 10.1371/journal.ppat.1002169. View

20.

Atkinson N, Witteveldt J, Evans D, Simmonds P . The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication. Nucleic Acids Res. 2014; 42(7):4527-45. PMC: 3985648. DOI: 10.1093/nar/gku075. View