Genomic organization of proviral PERV. (A) PERV displays genes for group specific antigen (gag), protease/polymerase polyprotein (pro/pol), and envelope protein (env), flanked by LTR. Both LTR and env vary significantly between individual proviruses, with the LTR determining the transcriptional activity and the envelope protein determining the host range with two polytropic virus classes, designated A and B. The gag and pol genes show only minor variations between proviruses. (B) Two different PERV LTR structures exist, one type harboring different numbers of a distinct 39-bp repeat in U3 (I to III) which is composed of subrepeat I (18 bp) and subrepeat II (21 bp) (26, 33). The second LTR type has no repeat structure, although sequences homologous to the subrepeats (designated Ia and IIa) can be found scattered across U3. The numbers given for each LTR designate the presence of proviral PERV LTR found in 21 BAC clones of a genomic large white library (26, 30). (C and D) Entropy plots for PERV envelope genes (panel C, PERV-A; panel D, PERV-B). For calculating entropy, all env sequences (see Appendix) were aligned, and the number of nucleotide differences was determined for every position. This difference is plotted against the position, thus indicating regions of high sequence variation. The sequence variation at the 3′ end of both env genes is caused by two factors. Since sequences used for entropy analysis were taken unmodified from GenBank, some truncated sequences led to an overall increase in diversity. The more important fact, however, is a structural divergence of the R-peptide structure of various PERV. This divergence corresponds in large part, but not exclusively, with the LTR structure (see “Phylogenetic analysis of env” in the text for details). Broadly striped arrowhead, hot spot with very high sequence variation; finely striped arrow head, variations at the C terminus of Env; cap, cap site; SD, splice donor; PBS, primer binding site; SA, splice acceptor; ppt, polypurine tract; p(A), poly adenylation site.