Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and kappa B regulatory elements.
Human immunodeficiency virus type 2 (HIV-2) displays several features which distinguish it from HIV-1. Among the differences in these two viruses are the responses of their enhancer regions to T-cell activation. For example, stimulation of HIV-1 transcription is largely dependent on two kappa B regulatory elements. In contrast, the HIV-2 enhancer has a single kappa B site and contains additional cis-acting sequences responsive to induction. One of these sites, previously termed CD3R, is a purine-rich site, also called PuB1, which is responsive to stimulation of the CD3 component of the T-cell receptor complex and binds Elf-1, a member of the ets proto-oncogene family. In this report, we examine the interaction of the PuB1 site with other sites in the HIV-2 enhancer. We demonstrate that the PuB1 site confers responsiveness to T-cell activators only in cooperation with additional enhancer elements. Induction of the HIV-2 enhancer is dependent on at least two other cis-acting regulatory elements in addition to PuB1 and kappa B. One of these elements is another purine-rich site (PuB2), which also binds recombinant Elf-1. An adjacent region, proximal to the PuB2 ets (pets) site, shows protection in DNase footprinting experiments with extracts from Jurkat T cells. Mutation of either the kappa B, PuB1, PuB2, or pets site significantly reduces the response of the HIV-2 enhancer to T-cell stimulation, an effect which is mediated at the RNA level. Therefore, activation of the HIV-2 enhancer is dependent on at least four cis-acting elements, only one of which is found in HIV-1, which act in synergy with one another. Despite their sequence similarity, the organization and function of the HIV-2 enhancer have diverged considerably from those of HIV-1.
Markovitz
D M
DM
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0680.
Smith
M J
MJ
Hilfinger
J
J
Hannibal
M C
MC
Petryniak
B
B
Nabel
G J
GJ
D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015498:HIV-2 / Q000235:genetics*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D013601:T-Lymphocytes / Q000382:microbiology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors