Open AccessRepair of a previously uncharacterized second host-range gene contributes to full replication of modified vaccinia virus Ankara (MVA) in human cells
Author(s) -
Chen Peng,
Bernard Moss
Publication year - 2020
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1921098117
Subject(s) - vaccinia , virology , biology , modified vaccinia ankara , gene , vector (molecular biology) , smallpox vaccine , viral replication , virus , permissive , replication (statistics) , cell culture , genetic enhancement , genetics , recombinant dna
Significance The highly attenuated vaccine vector MVA is an approved smallpox vaccine and is undergoing clinical trials as a vaccine vector for other infectious diseases. Although an inability to replicate in human cells contributes to the safety of MVA, the basis for its host restriction is not understood. Here we identify a host-range gene C16L/B22R, which is present as two copies in most orthopoxviruses but is inactivated in MVA. Repair of this gene allows replication of MVA in several tested human cell lines and, in combination with a second missing host-range gene C12L, restores full replication. Furthermore, a human cell line expressing both proteins is permissive for MVA. This knowledge may contribute to further engineering of MVA vaccines.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom