Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion

Nishant Kumar Ojha, Kavita S. Lole

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Hepatitis E Virus (HEV) is the major causative agent of acute hepatitis in developing countries. Its genome has three open reading frames (ORFs)—called as ORF1, ORF2, and ORF3. ORF1 encodes nonstructural polyprotein having multiple domains, namely: Methyltransferase, Y domain, Protease, Macro domain, Helicase, and RNA-dependent RNA polymerase. In the present study, we show that HEV-macro domain specifically interacts with light chain subunit of human ferritin (FTL). In cultured hepatoma cells, HEV-macro domain reduces secretion of ferritin without causing any change in the expression levels of FTL. This inhibitory effect was further enhanced upon Brefeldin-A treatment. The levels of transferrin Receptor 1 or ferroportin, two important proteins in iron metabolism, remained unchanged in HEV-macro domain expressing cells. Similarly, there were no alterations in the levels of cellular labile iron pool and reactive oxygen species, indicating that HEV-macro domain does not influence cellular iron homeostasis/metabolism. As ferritin is an acute-phase protein, secreted in higher level in infected persons and HEV-macro domain has the property of reducing synthesis of inflammatory cytokines, we propose that by directly binding to FTL, macro domain prevents ferritin from entering into circulation and helps in further attenuation of the host immune response.

Original languageEnglish
Pages (from-to)75-85
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume417
Issue number1-2
DOIs
StatePublished - 1 Jun 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016, Springer Science+Business Media New York.

Funding

Funding to carry out this research was provided by the intramural grant of the National Institute of Virology, Pune (Grant ID: HEP 1104). N.K.O. received graduate research fellowship from the Council of Scientific and Industrial Research, Government of India (Grant ID: 09/698[0015]/2009-EMR-1). We thank Dr. S. Emerson (NIH, USA) and Dr. X.J. Meng (Virginia Tech, Blacksburg, USA) for providing Huh-7: S10-3 cell line and HEV-luciferase subgenomic replicon, respectively.

FundersFunder number
Council of Scientific and Industrial Research, Government of India09/698[0015]/2009-EMR-1
National Institute of VirologyHEP 1104

    Keywords

    • Ferritin
    • Macrodomain
    • Nonstructural protein
    • Open reading frame 1

    Fingerprint

    Dive into the research topics of 'Hepatitis E virus ORF1 encoded macro domain protein interacts with light chain subunit of human ferritin and inhibits its secretion'. Together they form a unique fingerprint.

    Cite this