SIMIAN D RETROVIRUSES 4 & 5 SEQUENCE ANALYSES & IMPLICATIONS FOR DIVERGENCE

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Last year we reported the molecular cloning of D4/CYN/CA and D5/HRE/OR. We now describe the deduced amino acid sequence encoded by the complete D5/RHE/OR genome, and the sequence of the D4/CYN/CA env glycoprotein. The D5/RHE/OR genome contains the prototypical type D genetic structure (5'LTR-gag-prt-pol-env-3'LTR) and encodes a truncated 8045 bp provirus. The 5' LTR is 329 bp in length and possesses typical retroviral determinants of integration, replication and expression, including the U3, R and U5 regions, candidate TATA box and CAT sequences, and the potential polyadenylation signal. Interestingly, unlike all other molecularly-cloned SRVs, the D5/RHE/OR polyadenylation signal is identical to the signal found in most eukaryotic genes and in other viruses. The D5/RHE/OR gag gene encodes a polyprotein of 660 amino acids. As in all SRVs, the gag polyprotein contains the processed gag molecules p10, pp24/pp18, p12, p27, p14 and p4. The D5/RHE/OR viral protease is 314 amino acids long and contains a common Asp-Thr-Gly motif; the prt gene overlaps the gag gene by 61 residues, and the pol gene by 8 residues. The D5/RHE/OR pol gene encodes a product of 864 amino acids, which is 3 residues shorter than the pol products of other SRVs. The D5/RHE/OR env polyprotein is 585 amino acid residues long (gp70 and gp20 molecules are 394 and 191 amino acid residues, respectively), and contains 12 Asn-X-Ser(Thr) glycosylation sites, 11 of which are found within gp70. The D4/CYN/CA envelope polyprotein is 582 amino acids long (gp70 and gp20 molecules are 390 and 192 residues, respectively). The D4/CYN/CA gp70 and gp20 molecules are 61.8-68.7% (range) and 84.9-87.5% (range), similar to corresponding env glycoproteins identified for all other SRV serogroups. The comparison of D4/CYN/CA and D5/RHE/OR sequences to all other molecularly-cloned SRVs has provided valuable insight concerning the evolutionary divergence of the type D simian retrovirus family.