Selection of a subgroup A avian leukosis virus [ALV(A)] envelope resistantto soluble ALV(A) surface glycoprotein

The host developing resistance to retroviral infection is believed to be a major force in the evolution of multiple receptor usage by retroviruses. Th e avian leukosis-sarcoma virus (ALV) group of retroviruses provides a power ful system for studying the envelope-receptor interactions involved in retr ovirus entry; different members of this group of closely related viruses us e distinct cellular receptors. Analysis of the ALV envelope subgroups sugge sts that the different ALVs evolved from a common ancestor by mutations in the env gene. Cells and animals that express subgroup A ALV envelope glycop roteins are highly resistant to ALV(A) infection due to receptor interferen ce. In this study, we tested whether expression of a soluble form of subgro up A surface glycoprotein (SU) would result in receptor interference and wh ether this interference would select for resistant viruses with altered rec eptor usage. Chicken cells expressing the secreted ALV(A) SU Immunoadhesin SU(A)-rIgG, which contains the subgroup A SU domain fused to the constant r egion of a rabbit immunoglobulin (IgG) heavy chain, showed significant rece ptor interference. A variant virus resistant to SU(A)-rIgG receptor interfe rence was obtained. This virus had a six-amino-acid deletion in the subgrou p A hr1 that altered receptor usage. This approach may identify regions of SU that play a critical role in receptor specificity. (C) 2000 Academic Pre ss.