Cellular receptors are required for efficient entry of retroviruses in
to cells. We previously cloned a chicken gene responsible for suscepti
bility to the retrovirus subgroup A Rous sarcoma virus (RSV(A)). Here
we have isolated the quail homolog and generated two alternatively spl
iced processed genes encoding cellular receptors for RSV(A). Predicted
products of the processed genes appear to be small membrane-associate
d proteins with identical 83 amino acid extracellular domains but diff
erent membrane anchors. Within the extracellular domain is a region cl
osely related to the ligand-binding repeat of the low density lipoprot
ein receptor (LDLR). Expression of either processed gene renders mamma
lian cells specifically susceptible to RSV(A). Antibodies directed aga
inst the receptor block subgroup A infection of avian cells via endoge
nous receptors and have no effect on entry of other RSV subgroups. Thu
s, small LDLR-related proteins are cellular receptors for RSV(A).