A single-amino-acid substitution in the TvbS1 receptor results in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroups B and D and resistance to infection by subgroup E in vitro and in vivo.
The avian sarcoma and leukosis virus (ASLV) family of retroviruses contains five highly related envelope subgroups (A to E) thought to have evolved from a common viral ancestor in the chicken population. Three genetic loci in chickens determine the susceptibility or resistance of cells to infection by the subgroup A to E ASLVs. Some inbred lines of chickens display phenotypes that are somewhere in between either efficiently susceptible or resistant to infection by specific subgroups of ASLV. The tvb gene encodes the receptor for subgroups B, D, and E ASLVs. The wild-type Tvb(S1) receptor confers susceptibility to subgroups B, D, and E ASLVs. In this study, the genetic defect that accounts for the altered susceptibility of an inbred chicken line, line M, to infection by ASLV(B), ASLV(D), and ASLV(E) was identified. The tvb gene in line M, tvb(r2), encodes a mutant Tvb(S1) receptor protein with a substitution of a serine for a cysteine at position 125 (C125S). Here, we show that the C125S substitution in Tvb(S1) significantly reduces the susceptibility of line M cells to infection by ASLV(B) and ASLV(D) and virtually eliminates susceptibility to ASLV(E) infection both in cultured cells and in the incidence and growth of avian sarcoma virus-induced sarcomas in chickens. The C125S substitution significantly reduces the binding affinity of the Tvb(S1) receptor for the subgroup B, D, and E ASLV envelope glycoproteins. These are the first results that demonstrate a possible role of the cysteine-rich domain 3 in the function of the Tvb receptors.
Reinisová
Markéta
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ-14220 Prague 4, Czech Republic.
Senigl
Filip
F
Yin
Xueqian
X
Plachy
Jirí
J
Geryk
Josef
J
Elleder
Daniel
D
Svoboda
Jan
J
Federspiel
Mark J
MJ
Hejnar
Jirí
J
D000483:Alleles; D001355:Alpharetrovirus / Q000145:classification / Q000472:pathogenicity*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002642:Chick Embryo; D017931:DNA Primers; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012192:Retroviridae Infections / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014412:Tumor Virus Infections / Q000821:virology*
D017931:DNA Primers; D011991:Receptors, Virus