The family Poxpiridae contains two subfamilies: the Entomopoxvirinae (poxvi
ruses of insects) and the Chordopoxvirinae (poxviruses of vertebrates), Her
e we present the first characterization of the genome of an entomopoxvirus
(EPV) which infects the North American migratory grasshopper Melanoplus san
guinipes and other important orthopteran pests. The 236-kbp M. sanguinipes
EPV (MsEPV) genome consists of a central coding region bounded by 7-kbp inv
erted terminal repeats and contains 267 open reading frames (ORFs), of whic
h 107 exhibit similarity to previously described genes. The presence of gen
es not previously described in poxviruses, and in some cases in any other k
nown virus, suggests significant viral adaptation to the arthropod host and
the external environment. Genes predicting interactions with host cellular
mechanisms include homologues of the inhibitor of apoptosis protein, stres
s response protein phosphatase 2C, extracellular matrixin metalloproteases,
ubiquitin, calcium binding EF-hand protein, glycosyltransferase, and a tri
acylglyceride lipase, MsEPV genes with putative functions in prevention and
repair of DNA damage include a complete base excision repair pathway (urac
il DNA glycosylase, AP endonuclease, DNA polymerase beta, and an NAD(+)-dep
endent DNA ligase), a photoreactivation repair pathway (cyclobutane pyrimid
ine dimer photolyase), a LINE-type reverse transcriptase, and a mutT homolo
gue, The presence of these specific repair pathways may represent viral ada
ptation for repair of environmentally induced DNA damage. The absence of pr
eviously described poxvirus enzymes involved in nucleotide metabolism and t
he presence of a novel thymidylate synthase homologue suggest that MsEPV is
heavily reliant on host cell nucleotide pools and the de novo nucleotide b
iosynthesis pathway. MsEPV and lepidopteran genus B EPVs lack genome coline
arity and exhibit a low level of amino acid identity among homologous genes
(20 to 59%), perhaps reflecting a significant evolutionary distance betwee
n lepidopteran and orthopteran viruses. Divergence between MsEPV and the Ch
ordopoxvirinae is indicated by the presence of only 49 identifiable chordop
oxvirus homologues, low-level amino acid identity among these genes (20 to
48%), and the presence in MsEPV of 43 novel ORFs in five gene families. Gen
es common to both poxvirus subfamilies, which include those encoding enzyme
s involved in RNA transcription and modification, DNA replication, protein
processing, virion assembly, and virion structural proteins, define the gen
etic core of the Poxviridae.