J Virol. infected with RCASBP(B) alone, RCASBP(B)stva, or RCASBP(B)stva-mIgG were challenged separately with ALV(A) and ALV(C). Both sTva and sTva-mIgG significantly inhibited contamination by ALV(A) (95 and 100% respectively) but had no measurable effect on ALV(C) contamination. The results of this study indicate that a soluble receptor can effectively block contamination of at least some retroviruses and demonstrates the utility of the ALV experimental system in characterizing the mechanism(s) of viral entry. The first step in retrovirus infections involves an FN1 conversation between the viral envelope glycoprotein and a specific receptor on the surface of the host cell. A variety of cell surface proteins, including type I surface proteins, which span the Phenylbutazone (Butazolidin, Butatron) membrane once, and polytropic surface proteins, which span the membrane multiple occasions, have been identified as receptors for retroviruses (30). The avian leukosis-sarcoma computer virus (ALV) group of retroviruses provides a powerful model system for studying envelope-receptor interactions; different members of these closely related viruses use distinct cellular receptors to gain entry into cells. The members of the ALV group are classified into a number of envelope subgroups, designated A to J, on the basis of host range, cross-interference of contamination, and neutralization by antibodies (49). The susceptibility of chicken cells to ALV envelope subgroups A to E is determined by differences at three genetic loci designated receptor controls susceptibility to subgroup A ALV, the receptor controls susceptibility to subgroup C, and the receptor controls susceptibility to subgroups B, D, and E. Susceptibility or resistance to viral contamination is usually conferred by distinct alleles at each locus. There are two ways that resistance to retroviral contamination can occur at the cell surface: (i) the cell is usually genetically resistant, i.e., a functional version of the specific receptor is not present on the surface of the cell; and (ii) the receptors are saturated with viral envelope glycoproteins that actually block the receptor, a phenomenon known as receptor interference (30, 48, 49). Cells and animals that express retroviral envelope glycoproteins, due to a naturally occurring or genetically designed endogenous computer virus, are highly resistant to retroviruses using the same receptor and have less virus-associated pathogenesis. Based on the example of the resistance of chicken lines that express endogenous subgroup E envelope glycoproteins to ALV(E) contamination (38), Crittenden and colleagues exhibited that insertion of the ALV(A) envelope gene into the germ line of chickens and its subsequent expression provided resistance to contamination by ALV(A) strains by receptor interference (12, 18, 41, 42). However, the general power Phenylbutazone (Butazolidin, Butatron) of receptor interference as an antiviral strategy may be limited for retroviruses that express cytotoxic envelope glycoproteins (17, 21). Three cell surface proteins have been identified as ALV receptors: Tva, the receptor for ALV(A) (5, 6, 50); CAR1, the receptor for ALV(B) and ALV(D) (10, 45); and SEAR, the receptor for ALV(E) (1). The normal cellular function of the Tva receptor is currently unknown; however, the extracellular domain name contains Phenylbutazone (Butazolidin, Butatron) a 40-amino-acid region which is usually homologous to the ligand-binding region of the low-density lipoprotein receptor (7, 39, 40). To aid in the characterization of the interactions between Tva and the ALV(A) envelope glycoproteins, soluble forms of the 83-amino-acid extracellular domain name of the Tva receptor protein (sTva) were constructed by Connolly et al. (11), who reported that preincubation of the sTva proteins with different envelope subgroup ALVs caused a specific Phenylbutazone (Butazolidin, Butatron) block to contamination of susceptible chicken cells by ALV(A), but had no effect on ALV(B) or ALV(C) contamination. In a recent study, sTva produced and purified with a baculovirus expression system blocked contamination of turkey cells by ALV(A) (4). In this study, the interactions between the ALV(A) envelope glycoproteins and soluble forms of the receptor were analyzed in chicken cells in vitro and in vivo. To determine if cells and chickens expressing sTva proteins are resistant to ALV(A) contamination, ALV-based replication-competent retroviral vectors were used to efficiently deliver and express genes (20). The vectors are available with.