TY - CHAP
T1 - Type I Interferon
T2 - Monkeypox/Mpox Viruses Achilles Heel?
AU - Williams, Jacqueline
AU - Bonner, James
AU - Kibler, Karen
AU - Jacobs, Bertram L.
N1 - Publisher Copyright:
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024.
PY - 2024
Y1 - 2024
N2 - Poxviruses are notorious for having acquired/evolved numerous genes to counteract host innate immunity. Chordopoxviruses have acquired/evolved at least three different inhibitors of host necroptotic death: E3, which blocks ZBP1-dependent necroptotic cell death, and vIRD and vMLKL that inhibit necroptosis downstream of initial cell death signaling. While this suggests the importance of the necroptotic cell death pathway in inhibiting chordopoxvirus replication, several chordopoxviruses have lost one or more of these inhibitory functions. Monkeypox/mpox virus (MPXV) hasMonkeypox/mpox virus lost a portion of the N-terminus of its E3 homologue. The N-terminus of the vaccinia virus E3 homologue serves to inhibit activation of the interferon-inducible antiviral protein, ZBP1. This likely makes MPXV unique among the orthopoxvirusesOrthopoxviruses in being sensitive to interferonInterferon (IFN) treatment in many mammals, including humans, which encode a complete necroptotic cell death pathway. Thus, IFN sensitivity may be the Achille’s Heel for viruses like MPXV that cannot fully inhibit IFN-inducible, ZBP1-dependent antiviral pathways.
AB - Poxviruses are notorious for having acquired/evolved numerous genes to counteract host innate immunity. Chordopoxviruses have acquired/evolved at least three different inhibitors of host necroptotic death: E3, which blocks ZBP1-dependent necroptotic cell death, and vIRD and vMLKL that inhibit necroptosis downstream of initial cell death signaling. While this suggests the importance of the necroptotic cell death pathway in inhibiting chordopoxvirus replication, several chordopoxviruses have lost one or more of these inhibitory functions. Monkeypox/mpox virus (MPXV) hasMonkeypox/mpox virus lost a portion of the N-terminus of its E3 homologue. The N-terminus of the vaccinia virus E3 homologue serves to inhibit activation of the interferon-inducible antiviral protein, ZBP1. This likely makes MPXV unique among the orthopoxvirusesOrthopoxviruses in being sensitive to interferonInterferon (IFN) treatment in many mammals, including humans, which encode a complete necroptotic cell death pathway. Thus, IFN sensitivity may be the Achille’s Heel for viruses like MPXV that cannot fully inhibit IFN-inducible, ZBP1-dependent antiviral pathways.
KW - Interferon
KW - Monkeypox/mpox virus
KW - Orthopoxviruses
KW - RIPK3 (receptor-interacting protein kinase 3)
KW - Z-DNA
KW - Z-RNA
KW - ZBP1 (Z-DNA-binding protein 1)
UR - https://www.scopus.com/pages/publications/85194371572
UR - https://www.scopus.com/pages/publications/85194371572#tab=citedBy
U2 - 10.1007/978-3-031-57165-7_8
DO - 10.1007/978-3-031-57165-7_8
M3 - Chapter
C2 - 38801575
AN - SCOPUS:85194371572
T3 - Advances in Experimental Medicine and Biology
SP - 125
EP - 137
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -