Two different molecular defects in the Tva receptor gene explain the resistance of two tvar lines of chickens to infection by subgroup A avian sarcoma and leukosis viruses.
The subgroup A to E avian sarcoma and leukosis viruses (ASLVs) are highly related and are thought to have evolved from a common ancestor. These viruses use distinct cell surface proteins as receptors to gain entry into avian cells. Chickens have evolved resistance to infection by the ASLVs. We have identified the mutations responsible for the block to virus entry in chicken lines resistant to infection by subgroup A ASLVs [ASLV(A)]. The tva genetic locus determines the susceptibility of chicken cells to ASLV(A) viruses. In quail, the ASLV(A) susceptibility allele tva(s) encodes two forms of the Tva receptor; these proteins are translated from alternatively spliced mRNAs. The normal cellular function of the Tva receptor is unknown; however, the extracellular domain contains a 40-amino-acid, cysteine-rich region that is homologous to the ligand binding region of the low-density lipoprotein receptor (LDLR) proteins. The chicken tva(s) cDNAs had not yet been fully characterized; we cloned the chicken tva cDNAs from two lines of subgroup A-susceptible chickens, line H6 and line 0. Two types of chicken tva(s) cDNAs were obtained. These cDNAs encode a longer and shorter form of the Tva receptor homologous to the Tva forms in quail. Two different defects were identified in cDNAs cloned from two different ASLV(A)-resistant inbred chickens, line C and line 7(2). Line C tva(r) contains a single base pair substitution, resulting in a cysteine-to-tryptophan change in the LDLR-like region of Tva. This mutation drastically reduces the binding affinity of Tva(R) for the ASLV(A) envelope glycoproteins. Line 7(2) tva(r2) contains a 4-bp insertion in exon 1 that causes a change in the reading frame, which blocks expression of the Tva receptor.
Elleder
Daniel
D
Department of Cellular and Viral Genetics, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
Melder
Deborah C
DC
Trejbalova
Katerina
K
Svoboda
Jan
J
Federspiel
Mark J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D001353:Avian Leukosis / Q000276:immunology / Q000821:virology; D001354:Avian Leukosis Virus / Q000378:metabolism / Q000472:pathogenicity*; D030161:Avian Proteins; D001358:Avian Sarcoma Viruses / Q000378:metabolism / Q000472:pathogenicity*; D001483:Base Sequence; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens / Q000276:immunology* / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D011784:Quail; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001357:Sarcoma, Avian / Q000276:immunology / Q000821:virology; D017422:Sequence Analysis, DNA
D030161:Avian Proteins; D011991:Receptors, Virus; C088745:Tva receptor