Identification of New World Quails Susceptible to Infection with Avian Leukosis Virus Subgroup J

Abstract

The J subgroup of avian leukosis virus (ALV-J) infects domestic chickens, jungle fowl, and turkeys. This virus enters the host cell through a receptor encoded by the tvj locus and identified as Na ϩ /H ϩ exchanger 1. The resistance to avian leukosis virus subgroup J in a great majority of galliform species has been explained by deletions or substitutions of the critical tryptophan 38 in the first extracellular loop of Na ϩ /H ϩ exchanger 1. Because there are concerns of transspecies virus transmission, we studied natural polymorphisms and susceptibility/resistance in wild galliforms and found the presence of tryptophan 38 in four species of New World quails. The embryo fibroblasts of New World quails are susceptible to infection with avian leukosis virus subgroup J, and the cloned Na ϩ /H ϩ exchanger 1 confers susceptibility on the otherwise resistant host. New World quails are also susceptible to new avian leukosis virus subgroup J variants but resistant to subgroups A and B and weakly susceptible to subgroups C and D of avian sarcoma/leukosis virus due to obvious defects of the respective receptors. Our results suggest that the avian leukosis virus subgroup J could be transmitted to New World quails and establish a natural reservoir of circulating virus with a potential for further evolution.IMPORTANCE Since its spread in broiler chickens in China and Southeast Asia in 2000, ALV-J remains a major enzootic challenge for the poultry industry. Although the virus diversifies rapidly in the poultry, its spillover and circulation in wild bird species has been prevented by the resistance of most species to ALV-J. It is, nevertheless, important to understand the evolution of the virus and its potential host range in wild birds. Because resistance to avian retroviruses is due particularly to receptor incompatibility, we studied Na ϩ /H ϩ exchanger 1, the receptor for ALV-J. In New World quails, we found a receptor compatible with virus entry, and we confirmed the susceptibilities of four New World quail species in vitro. We propose that a prospective molecular epidemiology study be conducted to identify species with the potential to become reservoirs for ALV-J.KEYWORDS ALV-J, antiretroviral resistance, Na ϩ /H ϩ exchanger, New World quail, retroviral receptor T he range of hosts susceptible to a given retrovirus results from the process of coevolution between the viral envelope glycoproteins and host cell receptors. Selection forces imposed by the retrovirus drive the positive selection of receptors toward variants with decreased or even abrogated binding to retroviral envelopes. Vice versa, the highly error prone replication of retroviruses enables the rapid evolution of new strains with the capacity to bind to the variant receptors or even to quite new cell surface molecules. The results of these processes acting over evolutionary time are visible particularly in avian sarcoma/leukosis viruses (ASLVs), murine leukemia viruses (MLV), and feline leukemia viruses, where closely related virus subgroups differ in

Genetic Resistance to Avian Leukosis Viruses Induced by CRISPR/Cas9 Editing of Specific Receptor Genes in Chicken Cells

“…These virus-resistant alleles segregate in inbred lines of domestic chickens, which are thus resistant to the respective subgroup of ALV. All inbred lines and breeds of domestic chicken are susceptible to ALV-J but most of galliform birds which are closely related to domestic chickens are resistant due to the deletion of single amino-acid, tryptophan W38, of NHE1 [ 14 , 15 , 16 ]. Another source of mutations that affect the receptor function are chicken lines with decreased susceptibility to ALVs.…”

The Novel Avian Leukosis Virus Subgroup K Shares Its Cellular Receptor with Subgroup A

“…In addition, three species of New World quails, along with the common ringed-neck pheasant and gray partridge, displayed decreased susceptibility to RCASBP(JS11C1)GFP and complete or almost complete resistance to subgroup A. The resistance to subgroup A was previously described in New World quails and was attributed to W48S substitution within the specific Tva receptor (18). Interestingly, two closely related species of jungle fowls differed substantially, with the gray jungle fowl being infected efficiently with RCASBP(JS11C1)GFP but less efficiently with subgroup A (30% GFP-positive cells).…”

“…The host escapes this selection force via the evolution of receptor variants that exhibit decreased or even abrogated binding to retroviral envelopes. Numerous ALV-resistant receptor alleles have been described (5,(15)(16)(17), and positive selection was demonstrated to act within the extracellular loop 1 of NHE1, the critical region for ALV-J susceptibility (18). We have also identified receptor variants that lead to decreased susceptibility to avian sarcoma and leukosis virus (ASLV) infection (19,20).…”

A premature stop codon within the tvb receptor gene results in decreased susceptibility to infection by avian leukosis virus subgroups B, D, and E

“…The genetic defects in the resistant alleles can result in premature stop codons, frame-shift mutation or intronic deletions in the receptor genes [ 14 , 17 – 21 ], and substitutions of the critical amino acid residues in the receptor protein sequence [ 15 , 22 ]. Additionally, the deletion of the tryptophan 38 in the first extracellular loop of NHE1 receptor accounts for the resistance to ALV-J in galliform species [ 23 , 24 ]. Consequently, the resistant alleles not only confer host resistance to ALVs infection, but also provide valuable insight into antiviral strategies.…”