Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the orthomyxoviridae, Bunyaviridae, and filoviridae families

Amelia K. Pinto, Graham D. Williams, Kristy J. Szretter, James P. White, José Luiz Proença-Módena, Gai Liu, Judith Olejnik, James D. Brien, Hideki Ebihara, Elke Mühlberger, Gaya Amarasinghe, Michael S. Diamond, Adrianus C.M. Boon

Research output: Contribution to journalArticle

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Abstract

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'=-triphosphates (5'=-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5'=-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1-/- and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1-/- and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5'= ends of IAV gene segments. The affinity for 5'=-ppp RNA was approximately 10-fold lower than that for non-2=-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses.

Original languageEnglish (US)
Pages (from-to)9465-9476
Number of pages12
JournalJournal of Virology
Volume89
Issue number18
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Filoviridae
Bunyaviridae
RNA Viruses
Influenza A virus
Orthomyxoviridae
Oropouche virus
RNA
mice
La Crosse virus
Virus Diseases
Infection
California encephalitis virus
infection
Virus Attachment
proteins
oligonucleotides
Oligonucleotides
Antiviral Agents
RNA Caps
Ebolavirus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Pinto, A. K., Williams, G. D., Szretter, K. J., White, J. P., Proença-Módena, J. L., Liu, G., ... Boon, A. C. M. (2015). Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the orthomyxoviridae, Bunyaviridae, and filoviridae families. Journal of Virology, 89(18), 9465-9476. https://doi.org/10.1128/JVI.00996-15

Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the orthomyxoviridae, Bunyaviridae, and filoviridae families. / Pinto, Amelia K.; Williams, Graham D.; Szretter, Kristy J.; White, James P.; Proença-Módena, José Luiz; Liu, Gai; Olejnik, Judith; Brien, James D.; Ebihara, Hideki; Mühlberger, Elke; Amarasinghe, Gaya; Diamond, Michael S.; Boon, Adrianus C.M.

In: Journal of Virology, Vol. 89, No. 18, 01.01.2015, p. 9465-9476.

Research output: Contribution to journalArticle

Pinto, AK, Williams, GD, Szretter, KJ, White, JP, Proença-Módena, JL, Liu, G, Olejnik, J, Brien, JD, Ebihara, H, Mühlberger, E, Amarasinghe, G, Diamond, MS & Boon, ACM 2015, 'Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the orthomyxoviridae, Bunyaviridae, and filoviridae families', Journal of Virology, vol. 89, no. 18, pp. 9465-9476. https://doi.org/10.1128/JVI.00996-15
Pinto, Amelia K. ; Williams, Graham D. ; Szretter, Kristy J. ; White, James P. ; Proença-Módena, José Luiz ; Liu, Gai ; Olejnik, Judith ; Brien, James D. ; Ebihara, Hideki ; Mühlberger, Elke ; Amarasinghe, Gaya ; Diamond, Michael S. ; Boon, Adrianus C.M. / Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the orthomyxoviridae, Bunyaviridae, and filoviridae families. In: Journal of Virology. 2015 ; Vol. 89, No. 18. pp. 9465-9476.
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