A role for Z-DNA binding in vaccinia virus pathogenesis.
The N-terminal domain of the E3L protein of vaccinia virus has sequence similarity to a family of Z-DNA binding proteins of defined three-dimensional structure and it is necessary for pathogenicity in mice. When other Z-DNA-binding domains are substituted for the similar E3L domain, the virus retains its lethality after intracranial inoculation. Mutations decreasing Z-DNA binding in the chimera correlate with decreases in viral pathogenicity, as do analogous mutations in wild-type E3L. A chimeric virus incorporating a related protein that does not bind Z-DNA is not pathogenic, but a mutation that creates Z-DNA binding makes a lethal virus. The ability to bind the Z conformation is thus essential to E3L activity. This finding may allow the design of a class of antiviral agents, including agents against variola (smallpox), which has an almost identical E3L.
Kim
Yang-Gyun
YG
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 68-233, Cambridge, MA 02139-4307, USA.
Muralinath
Maneesha
M
Brandt
Teresa
T
Pearcy
Matthew
M
Hauns
Kevin
K
Lowenhaupt
Ky
K
Jacobs
Bertram L
BL
Rich
Alexander
A
D000243:Adenosine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002678:Chimera / Q000235:genetics; D004279:DNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014774:Virulence
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C081374:E3L protein, Vaccinia virus; D006023:Glycoproteins; C498634:Igf2bp1 protein, rat; D016601:RNA-Binding Proteins; D014764:Viral Proteins; C402632:Zbp1 protein, mouse; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase