Structure of the Long Terminal Repeat of Simian Lymphotropic Virus Type III (African Green Monkey) and Its Relatedness to That of HIV

Abstract

The simian T-lymphotropic virus type III (STLV-III[AGM]) is a retrovirus in wild African green monkeys which is serologically related to the human Tlymphotropic virus type III (HTLV-III/LAV-1/HIV) and other related human retroviruses. The long terminal repeats (LTR) contained in clones of viral DNA of (STLV-III[AGM]) were subcloned in M13 and their DNA sequence was determined and compared with that of HIV (HTLV-III[BH10]). The STLV-III(AGM) LTR is considerably larger than that of HTLV-III(BH1O) (800 bp vs 634 bp) and contains a 498 bp U3 region, a 176 bp R region, and a 126 bp U5 region. These two LTR sequences share regions of significant homology. Regions of greatest homology include the 5, portion of U3, a core enhancer sequence in U3, sequences including and surrounding the TATAA promoter box in U3 and the AATAAA polyadenylation/termination signal in R, and the 3′-most region of U5. The relatively larger size of the STLV-III LTR is due to the presence in all three parts of the LTR of sequences which have no apparent homolog in the HIV LTR. Overall, the two LTRs are 47% homologous. Even greater homology (75%) is evident with a 300 bp segment including R and some of U3 from the LTR of another human retrovirus, HIV-2/LAV-2. The STLV-III LTR contains an imperfect 28 bp direct repeat in the R region which is not present in HIV. There are no obvious direct repeats in U3 homologous to the 10 bp repeat in the U3 of HTLV-III. The polypurine tract preceding the downstream LTR is identical to that of HTLV-III and the DNA sequence of the primer binding site 3′ of the upstream LTR indicates that STLV-III, like HIV, equine infectious anemia virus, and the murine mammary tumor virus, uses tRNA-_lys3 as its primer. (Visna virus, simian type D retroviruses, and caprine arthritis and encephalitis virus use a different isoaccepting species of tRNA-_lys as a primer.) The data indicate that among the known retroviruses, STLV-III(AGM) is most closely related to HIV and HIV-2/ LAV-2, confirming predictions based on serologic cross-reactions of some of the virus structural proteins and showing that it is related to the lentivirus family. The degree of difference between the two viruses, however, suggests that HIV did not likely originate directly or recently from STLV-III(AGM) via transmission from monkeys.