L. Zsak et al., AN AFRICAN SWINE FEVER VIRUS VIRULENCE-ASSOCIATED GENE NL-S WITH SIMILARITY TO THE HERPES-SIMPLEX VIRUS ICP34.5 GENE, Journal of virology, 70(12), 1996, pp. 8865-8871
We described previously an African swine fever virus (ASFV) open readi
ng frame, 23-NL, in the African isolate Malawi Lil 2011 whose product
shared significant similarity in a carboxyl-terminal domain with those
of a mouse myeloid differentiation primary response gene, MyD116, and
the herpes simplex virus neurovirulence-associated gene, ICP34.5 (M.
D. Sussman, Z. Lu, G. Kutish, C. L. Afonso, P. Roberts, and D. L. Rock
, J. Virol. 66:5586-5589, 1992). The similarity of 23-NL to these gene
s suggested that this gene may function in some aspect of ASFV virulen
ce and/or host range. Sequence analysis of additional pathogenic viral
isolates demonstrates that this gene is highly conserved among divers
e ASFV isolates and that the gene product exists in either a long (184
amino acids as in 23-NL) or a short form (70 to 72 amino acids in oth
er examined ASFV isolates). The short form of the gene, NL-S, encodes
the complete highly conserved, hydrophilic, carboxyl-terminal domain o
f 56 amino acids common to 23-NL, MyD116, and ICP34.5. Recombinant NL-
S gene deletion mutants and their revertants were constructed from the
pathogenic ASFV isolate E70 and an E70 monkey cell culture-adapted vi
rus, MS44, to study gene function, Although deletion of NL-S did not a
ffect viral growth in primary swine macrophages or Vero cell cultures
in vitro, the null mutant, E70/43, exhibited a marked reduction in pig
virulence, In contrast to revertant or parental E70 where mortality w
as 100%, all E70/43-infected animals survived infection, With the exce
ption of a transient fever response, E70/43-infected animals remained
clinically normal and exhibited a 1,000-fold reduction in both mean an
d maximum viremia titers. All convalescent E70/43-infected animals sur
vived infection when challenged with parental E70 at 30 days postinfec
tion. These data indicate that the highly conserved NL-S gene of ASFV,
while nonessential for growth in swine macrophages in vitro, is a sig
nificant viral virulence factor and may function as a host range gene.