Sh. Lee et al., Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily, NAT GENET, 28(1), 2001, pp. 42-45
Cytomegalovirus is the leading cause of congenital viral disease and the mo
st important opportunistic infection in immunocompromised patients(1,2). We
have used a mouse experimental infection model (MCMV) to study the genetic
parameters of host/virus interaction. Susceptibility to infection with MCM
V is controlled by Cmv1, a chromosome 6 locus that regulates natural killer
(NK) cell activity against virally infected targets(3-5). Here, we use a p
ositional cloning strategy to isolate the gene mutated at the Cmv1 locus. C
mv1 maps within a 0.35-cM interval defined by markers D6Ott8 and D6Ott115,
which corresponds to a physical distance of 1.6 Mb (refs. 6-8). A transcrip
t map of the region identified 19 genes(8), including members of the killer
cell lectin-like receptor family a (Klra, formerly Ly49; refs. 9-12), whic
h encode inhibitory or activating NK cell receptors that interact with MHC
class I molecules(13-15). Klra genes have different copy numbers and genomi
c organization, and are highly polymorphic among inbred strains, making it
difficult to distinguish between normal allelic variants and distinct Klra
genes(15-17), or possible mutations associated with Cmv1. The recombinant i
nbred strain BXD-8/Ty (BXD-8; ref. 18), derived from Cmv1(r) C57BL/6 (B6, r
esistant) and Cmv1(s) DBA/2 (susceptible), is of particular interest becaus
e it is highly susceptible to MCMV infection despite having a B6 haplotype
at Cmv1, We determined that MCMV susceptibility in BXD-8 is associated with
the deletion of Klra8 (formerly Ly49h).