Molecular basis of host range variation in avian retroviruses

Previous genetic analysis has localized the region of the Rous sarcoma virus (RSV) env gene responsible for host range specificity to that encoding the middle one-third of gp85. To better understand the host range determinants, the relevant regions of the genomes of infectious molecular clones of the transformation-defective Prague strain of RSV, subgroup B (Pr-RSV-B) and Rous-associated virus 0 (RAV-0) (subgroup E) were sequenced and compared with the sequence of Pr-RSV-C. This comparative analysis identified two variable regions of low amino acid sequence homology flanked by highly conserved amino acid sequences. The first variable region (hr1) begins at base 5654 in the Pr-RSV-C sequence and encodes 32 amino acids. The second variable region (hr2) begins at base 5846 and encodes 27 amino acids. To test the role of the variable regions in host range specificity, we determined the sequence of this region of the env gene of NTRE-4, a recombinant virus between Pr-RSV-B and RAV-0 which exhibits an extended host range. This analysis revealed that the recombinant subgroup-encoding region of NTRE-4 is composed of 200 bases of RAV-0 sequence, including hr2, flanked by sequences which are otherwise of Pr-RSV-B origin. This study indicates that hr1 and hr2 are the domains of gp85 responsible for host range determination in avian retroviruses.