Functional analysis of the Tat trans activator of human immunodeficiency virus type 2.
The trans-activator (Tat) proteins of the related but distinct type 1 and type 2 human immunodeficiency viruses (HIV-1 and HIV-2) display incomplete functional reciprocity. One possible explanation of this observation, suggested by computer analysis of potential RNA secondary structures within the viral trans-activation response (TAR) elements, is that HIV-2 Tat requires the presentation of two viral RNA stem-loop sequences for full activity whereas HIV-1 Tat is maximally active upon presentation of a single stem-loop structure. Here, we demonstrate that the HIV-2 long terminal repeat indeed contains two functionally independent TAR elements. However, the second (3') TAR element of HIV-2 is significantly less active than the 5' TAR element and is functionally masked in the context of an intact HIV-2 long terminal repeat. Evidence is presented suggesting that the activities of these two HIV-2 TAR elements reflect, at least in part, their relative distances from the site of transcription initiation. Although the HIV-2 TAR element proximal to the viral mRNA cap site appears to be sufficient for effective trans activation by HIV-2 Tat in vitro, this functional redundancy may nevertheless serve to enhance HIV-2 replication in infected cells in vivo.
Fenrick
R
R
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Malim
M H
MH
Hauber
J
J
Le
S Y
SY
Maizel
J
J
Cullen
B R
BR
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D015696:Gene Products, tat / Q000235:genetics*; D015756:Genes, tat; D015498:HIV-2 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D014775:Virus Activation / Q000235:genetics; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus