Three amino acid mutations (F51L, T59A, and S390L) in the capsid protein of the hepatitis E virus collectively contribute to virus attenuation.

Journal of Virology
Laura CórdobaXiang-Jin Meng

Abstract

Hepatitis E virus (HEV) is an important but extremely understudied human pathogen, and the mechanisms of HEV replication and pathogenesis are largely unknown. We previously identified an attenuated genotype 3 HEV mutant (pSHEV-1) containing three unique amino acid mutations (F51L, T59A, and S390L) in the capsid protein. To determine the role of each of these mutations, we constructed three HEV single mutants (rF51L, rT59A, and rS390L) which were all found to be replication competent in Huh7 liver cells. To determine the pathogenicities of the mutants, we utilized the specific-pathogen-free (SPF) pig model for HEV and a unique inoculation procedure that bypasses the need for propagating infectious HEV in vitro. A total of 60 pigs were intrahepatically inoculated, via an ultrasound-guided technique, with in vitro-transcribed full-length capped RNA transcripts from the infectious clones of each single mutant, the pSHEV-1 triple mutant, wild-type pSHEV-3, or phosphate-buffered saline (PBS) buffer (n = 10). The results showed that the F51L mutation partially contributed to virus attenuation, whereas the T59A and S390L mutations resulted in more drastic attenuation of HEV in pigs, as evidenced by a significantly lower incidence of vi...Continue Reading

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Citations

Mar 23, 2012·Journal of Virology·Yogesh A Karpe, Xiang-Jin Meng
Jun 18, 2014·ILAR Journal·Danielle M YugoXiang-Jin Meng
Apr 28, 2012·Gastroenterology·Heiner WedemeyerMichael P Manns
Jun 21, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Jayanta BorkakotiPremashis Kar
Aug 17, 2016·EBioMedicine·Hoang van TongThirumalaisamy P Velavan
Jan 8, 2014·Clinical Microbiology Reviews·Lisa J KrainAlain B Labrique
Aug 1, 2012·Emerging Microbes & Infections·Dianjun Cao, Xiang-Jin Meng
Aug 21, 2020·Current Opinion in Virology·Johannes ScholzReimar Johne
May 18, 2021·Computational and Structural Biotechnology Journal·Bo Wang, Xiang-Jin Meng

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