Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes

Autor: Brian Wigdahl, Maureen M. Goodenow, Fred C. Krebs, Steven M. Pomeroy, Dorothy Mehrens
Rok vydání: 1998
Předmět:
Adult
Chloramphenicol O-Acetyltransferase
Transcription
Genetic
Lymphoid Enhancer-Binding Factor 1
viruses
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Activating transcription factor
Astrocytoma
Transfection
Virus Replication
CREB
Jurkat cells
Jurkat Cells
Proviruses
Genes
Reporter
Tumor Cells
Cultured
Humans
Pharmacology (medical)
Lymphocytes
Cyclic AMP Response Element-Binding Protein
Molecular Biology
Transcription factor
CAMP response element binding
HIV Long Terminal Repeat
Acquired Immunodeficiency Syndrome
Binding Sites
Base Sequence
biology
General transcription factor
Biochemistry (medical)
NF-kappa B
Nuclear Proteins
Cell Biology
General Medicine
Molecular biology
Long terminal repeat
DNA-Binding Proteins
DNA binding site
HIV-1
biology.protein
Oligonucleotide Probes
Neuroglia
Sequence Alignment
Transcription Factors
Zdroj: Journal of Biomedical Science. 5:31-44
ISSN: 1423-0127
1021-7770
Popis: The generation of genomic diversity during the course of infection has the potential to affect all aspects of HIV-1 replication, including expression of the proviral genome. To gain a better understanding of the impact of long terminal repeat (LTR) sequence diversity on LTR-directed gene expression in cells of the central nervous system (CNS) and immune system, we amplified and cloned LTRs from proviral DNA in HIV-1-infected peripheral blood. Sequence analysis of nineteen LTRs cloned from 2 adult and 3 pediatric patients revealed an average of 33 nucleotide changes (with respect to the sequence of the LAI LTR) within the 455-bp U3 region. Transient expression analyses in cells of neuroglial and lymphocytic origin demonstrated that some of these LTRs had activities which varied significantly from the LAI LTR in U-373 MG cells (an astrocytoma cell line) as well as in Jurkat cells (a CD4-positive lymphocyte cell line). While LTRs which demonstrated the highest activities in U-373 MG cells also yielded high activities in Jurkat cells, the LTRs were generally more active in Jurkat cells when compared to the LAI LTR. Differences in LTR sequence also resulted in differences in transcription factor recruitment to cis-acting sites within the U3 region of the LTR, as demonstrated by electrophoretic mobility shift assays. In particular, naturally occurring sequence variation impacted transcription factor binding to an activating transcription factor/cAMP response element binding (ATF/CREB) binding site (located between the LEF-1 and distal NF-kappaB transcription factor binding sites) that we identified in previous studies of the HIV-1 LTR. These findings suggest that LTR sequence changes can significantly affect basal LTR function and transcription factor recruitment, which may, in turn, alter the course of viral replication in cells of CNS and immune system origin.
Databáze: OpenAIRE
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