Induction of AIDS by simian immunodeficiency virus lacking NF-kappaB and SP1 binding elements.
Rhesus monkeys (Macaca mulatta) were infected with five strains of simian immunodeficiency virus (SIV) derived from SIVmac239 containing deletions (delta) or substitutions (subst) in NF-kappaB and Sp1 binding sites. We have shown previously that mutations in these regions still allow efficient SIVmac replication in primary lymphoid cell cultures (P. O. Ilyinskii and R. C. Desrosiers, J. Virol. 70:3118-3126, 1996). Two animals were inoculated intravenously with each mutant strain of SIVmac239: delta NFkappaB, delta Sp1234, delta NFkappaB delta Sp1234, substSp12, and substSp1234. All but one of the infected animals showed an early spike in plasma antigenemia, maintained high virus burdens, and had significant changes in lymphoid tissues, and six died with AIDS within the first 60 weeks of infection. One of the animals infected with the SIV strain delta NFkappaB delta Sp1234 showed lower levels of plasma antigenemia and lower virus burdens; the other animal infected with this same mutant strain died with AIDS 17 weeks after inoculation. No consistent novel mutations or reversions were detected in proviral sequences derived from the animals infected with the deletion mutants and the substSp12 mutant by 20 weeks postinfection. Point-mutated sequences were partially deleted in both animals infected with the substSp1234 strain. These results indicate that the NF-kappaB and Sp1 binding sites are not essential for the induction of AIDS by SIVmac239. They also provide indirect evidence for the importance of a novel enhancer element in the U3 region of the SIVmac long terminal repeat that is located immediately upstream of the NF-kappaB binding site within the C-terminal region of the nef coding sequence.
Ilyinskii
P O
PO
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
Simon
M A
MA
Czajak
S C
SC
Lackner
A A
AA
Desrosiers
R C
RC
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000097:blood; D001665:Binding Sites; D002460:Cell Line; D018450:Disease Progression; D015683:Gene Products, gag / Q000097:blood; D008253:Macaca mulatta; D016296:Mutagenesis; D016328:NF-kappa B / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology; D016329:Sp1 Transcription Factor / Q000378:metabolism*
D000914:Antibodies, Viral; D000956:Antigens, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D016328:NF-kappa B; D016329:Sp1 Transcription Factor