Adeno-associated virus type 2-mediated inhibition of human immunodeficiency virus type 1 (HIV-1) replication: involvement of p78rep/p68rep and the HIV-1 long terminal repeat.
Microinjection of wild-type adeno-associated virus type 2 (AAV-2) DNA and infectious human immunodeficiency virus type 1 (HIV-1) proviral DNA into the nuclei of human epithelioid SW480 cells leads to specific inhibition of HIV-1 replication. Mutational analysis of the AAV genome showed that this negative interference can be assigned to a functional AAV-2 rep gene. Moreover, the p78rep/p68rep proteins are sufficient for the anti-HIV-1 effects. The rep gene also inhibits the expression of a chloramphenicol acetyl-transferase (CAT) gene driven by the U3/R portion of the HIV-1 long terminal repeat (LTR) in the absence of tat expression. This suggests that the U3/R portion of HIV-1 contains elements responsible for the AAV-2 rep-mediated inhibition of HIV-1 LTR-driven CAT gene expression and, probably, also of HIV-1 replication. The results add support for the general significance of AAV-2 and specifically the rep gene as tools for down-regulating heterologous gene expression.
Rittner
K
K
Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Heilbronn
R
R
Kleinschmidt
J A
JA
Sczakiel
G
G
D001483:Base Sequence; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D000229:Dependovirus / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis; D014762:Viral Interference / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; C068734:rep proteins, Adeno-associated virus 2