Molecular Clones from a Non-Acutely Pathogenic Derivative of SIVsmmPBj14: Characterization and Comparison to Acutely Pathogenic Clones

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Abstract
Molecularly cloned simian immunodeficiency viruses capable of inducing acute, fatal disease in pig-tailed macaques had been derived previously from a biological clone (bcl-3) of the PBJ14 isolate of SIV from sooty mangabey monkeys (SIVsmmPBj14). The present study was undertaken in order to characterize virus from a second biological clone of SIVsmmpBjl4, bcl-1, which fails to induce acute or fatal disease. Polymerase chain reaction was used to amplify 5′ and 3′ viral genome halves. The DNA sequence of two 3′ halves was determined, and an infectious recombinant generated using a bcl-3-derived 5′ half and a bcl-1-derived 3′ half. Overall, bcl-1and bcl-3-derived viruses displayed close homology, differing by a total of 2% at the DNA level and 1-6% at the amino acid level within the 8 open reading frames examined. In contrast to the bcl-3-derived viruses, the bcl-1-derived viruses encode a truncated transmembrane envelope glycoprotein. Another consistent difference was the presence of a 22 bp duplication in the U3 portion of the long terminal repeat (LTR) of bcl-3-derived viruses that includes the NFκB transcriptional enhancer binding site. To assess the importance of this duplication, virus chimeras were generated which removed the duplication from the 3′-LTR or from both LTRs of a bcl-3 clone. The former virus was unstable, reacquiring the duplication through recombination with the 5′ LTR. No consistent difference were observed, however, between viruses with or without the duplication in the in vitro studies conducted to date. Thus, the role of the LTR duplication in disease induction, if any, remains to be established.