The Receptor for the Subgroup C Avian Sarcoma and Leukosis Viruses, Tvc, Is Related to Mammalian Butyrophilins, Members of the Immunoglobulin Superfamily

Abstract

The five highly related envelope subgroups of the avian sarcoma and leukosis viruses (ASLVs), subgroup A [ASLV(A)] to ASLV(E), are thought to have evolved from an ancestral envelope glycoprotein yet utilize different cellular proteins as receptors. Alleles encoding the subgroup A ASLV receptors (Tva), members of the low-density lipoprotein receptor family, and the subgroup B, D, and E ASLV receptors (Tvb), members of the tumor necrosis factor receptor family, have been identified and cloned. However, alleles encoding the subgroup C ASLV receptors (Tvc) have not been cloned. Previously, we established a genetic linkage between tvc and several other nearby genetic markers on chicken chromosome 28, including tva. In this study, we used this information to clone the tvc gene and identify the Tvc receptor. A bacterial artificial chromosome containing a portion of chicken chromosome 28 that conferred susceptibility to ASLV(C) infection was identified. The tvc gene was identified on this genomic DNA fragment and encodes a 488-amino-acid protein most closely related to mammalian butyrophilins, members of the immunoglobulin protein family. We subsequently cloned cDNAs encoding Tvc that confer susceptibility to infection by subgroup C viruses in chicken cells resistant to ASLV(C) infection and in mammalian cells that do not normally express functional ASLV receptors. In addition, normally susceptible chicken DT40 cells were resistant to ASLV(C) infection after both tvc alleles were disrupted by homologous recombination. Tvc binds the ASLV(C) envelope glycoproteins with low-nanomolar affinity, an affinity similar to that of binding of Tva and Tvb with their respective envelope glycoproteins. We have also identified a mutation in the tvc gene in line L15 chickens that explains why this line is resistant to ASLV(C) infection.Retroviruses require an interaction between the viral glycoproteins and a specific cell surface protein (receptor) to initiate entry into a cell (reviewed in references 32 and 56). The envelope glycoproteins of retroviruses are composed of trimers of two glycoproteins: the surface glycoprotein (SU), which contains the domains responsible for interaction with the host receptor, and the transmembrane glycoprotein (TM), which anchors SU to the membrane and mediates fusion of the viral and host membranes. The interaction of the SU glycoprotein with the host receptor usually involves multiple, noncontiguous determinants in both proteins that specify receptor choice and binding affinity and trigger a conformational change in the envelope glycoproteins that initiates the fusion process. Despite the complexity and specificity of the interaction between the viral glycoproteins and host receptors, closely related retroviruses carry envelope glycoproteins with mutations that alter receptor usage. The natural selection of retroviral subgroups with altered receptor usage may help the virus overcome host resistance and promote coinfection and may lead to heterotransmission.The five highly related envelope subgroups of...

Regulation of Immunity by Butyrophilins

“…Resistance to the T cell lymphomas induced in unimmunized chickens by infection with the herpesvirus GaHV-2 (Marek's disease virus) has been linked to the polymorphic BG1 locus (131). In addition, a separate chicken butyrophilin-like gene, Tvc-1, has been described as the receptor for avian leukosis virus (132). In summary, chicken BG genes are an extensive, highly polymorphic gene family with poorly understood functions.…”

BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

“…The IgV domains of murine MOG and murine BTN1A1 share 44% amino acid identity, and treatment of rodents with a preparation of the IgV domain of bovine BTN1A1 has been shown to modulate the symptoms of experimental autoimmune encephalomyelitis (EAE), a disease model of MS (17,18). BTNrelated proteins in avian species include the chicken BG molecules, which are encoded in the extended BF/BL region of the MHCcontaining B complex (19) and the Tvc gene, which is a receptor for subgroup C avian sarcoma and leukosis viruses (20).…”

Retrovirus-mediated in vitro gene transfer into chicken male germ line cells

“…ASLV-derived replication-defective vectors could be used for this purpose as well; however, the sensitivity of particular chicken breeds to individual ASLV subgroups (A-E, J; Barnard et al 2006) should be tested. Expression of Tva and Tvb but not Tvc receptor genes was shown in the testes (Elleder et al 2005), but their expression in spermatogonia remains to be characterized. Secondly, the recovery of spermatogenesis by donor cells can be established only from rare SSCs.…”