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Transcription from the human immunodeficiency virus type 1 (HIV-1) provirus is activated by a cellular factor, NF kappa B, recognizing the tandemly repeated 10-base-pair sequences, termed the kappa B sequence, present in the enhancer region within the viral long terminal repeat (LTR). Using electrophoretic mobility shift assay (EMSA), which demonstrates specific DNA-protein interaction in vitro, we could demonstrate that reducto-oxidative modulation of NF kappa B dramatically changes its DNA binding activity and that a cellular physiological reducing catalyst, thioredoxin (TRX) also known as adult T cell leukemia derived factor (ADF), fully restored the DNA-binding activity of the oxidized NF kappa B. We also observed that purified TRX/ADF protein could augment gene expression from HIV LTR as demonstrated by transient chloramphenicol acetyltransferase (CAT) assay. These observations confirmed the previous notion that ADF might be an inducing factor of cellular interleukin-2 receptor alpha subunit (IL-2R alpha) through the kappa B sequence that is a common central cis-regulatory element in both IL-2R alpha and HIV gene expression. These observations indicate that reducto-oxidative regulation (or redox regulation) of a cysteine residue(s) on the NF kappa B molecule might play an important role in its specific DNA interaction and that it might provide a clue to the understanding of a pathway of cellular signal transduction to NF kappa B that is independent from the known pathways involving protein phosphorylation.

A region of human immunodeficiency virus type 1 (HIV‐1) genomic RNA known to interact with the viral nucleocapsid protein is one of the crucial components for retroviral genomic RNA packaging. We have investigated the secondary structure for this RNA packaging signal of HIV‐1 using RNA mapping techniques and extensive computer analyses. Our results suggest that the RNA sequence containing the packaging signal conforms to a stable stem‐loop structure and that a portion of this structure is conserved among twenty independent HIV‐1 isolates. The heterogeneity of the RNA packaging sequence was not correlated with the amino acid sequence variability of the viral nucleocapsid protein. These findings have critical implication in understanding the viral maturation process.

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