Page:Interim Staff Report on Investigation into Risky MPXV Experiment at the National Institute of Allergy and Infectious Diseases.pdf/70

 the evolution of ORPV. Most of the accessory genes were acquired in three major waves antedating the origin of ORPV from chordopoxviruses. The evolution of ORPV themselves was dominated by gene loss, with numerous genes lost at the base of each major group of ORPV. Examination of pairs of ORPV accessory genes that were either often or rarely lost concurrently during ORPV evolution allowed prediction of different types of functional interactions.

The MVA host range restriction is exceptional in that synthesis of the abundant viral proteins appears unaffected, but morphogenesis of virus particles is abortive. Despite the importance of the host range restriction for vaccine safety, the basis for this antiviral effect has remained an enigma. We demonstrated that the zinc finger antiviral protein (ZAP) is a specific host restriction factor for replication of MVA in human cells. Moreover, the intact vaccinia virus C16 protein, which was disrupted during the attenuation of MVA, sequesters ZAP in cytoplasmic punctae, and effectively counteracts the inhibitory effects of ZAP.

Publications Generated during the 2021 Reporting Period

2/2
 * 1) Senkevich TG, Yutin N, Wolf YI, Koonin EV, Moss B (2021). Ancient Gene Capture and Recent Gene Loss Shape the Evolution of Orthopoxvirus-Host Interaction Genes. mBio 12, e0149521. https://doi.org/10.1128/mBio.01495-21
 * 2) Peng C, Wyatt LS, Glushakow-Smith SG, Lal-Nag M, Weisberg AS, Moss B (2020). Zinc-finger antiviral protein (ZAP) is a restriction factor for replication of modified vaccinia virus Ankara (MVA) in human cells. PLoS Pathog 16, e1008845. https://doi.org/10.1371/journal.ppat.1008845