Recent studies indicate that human immunodeficiency virus type 1 (HIV) gene expression can be dramatically enhanced by certain heterologous viral and chemical agents, implicating these as potential reactivating agents of latent virus infection. A common denominator shared by these agents is their ability to cause stress responses in cells. In an effort to determine whether stress responses affect HIV gene expression, we examined the effects of ultraviolet light (UV) and mitomycin C, on HIV gene expression as well as on viral growth and development. We demonstrate that these agents enhance HIV gene expression up to 150-fold. These levels are similar to those obtained by the tat gene product, the HIV trans-activating factor responsible for enhancing viral gene expression. The increase in gene expression after UV irradiation appears to require transcription but not de novo protein synthesis, and correlates with an accumulation of stable mRNA. Most importantly, UV irradiation of human T-cells prior to viral infection significantly shortens the viral growth cycle. Apparently, UV-induced cellular stress is highly conducive for viral replication and growth. We further demonstrate that even direct sunlight can activate HIV gene expression. These results demonstrate that DNA damaging agents, and perhaps other agents which elicit SOS-like stress responses in mammalian cells, can activate HIV expression thereby enhancing viral replication and development.

The induction of immune responses in vivo is typically performed with antigens administered in external adjuvants, like alum, complete Freund's adjuvant, LPS and, more recently, monophosphoryl lipid A (MPL). However, the role of the adjuvant is still poorly defined. The aim of this study was to test whether the MPL affects the function of antigen-presenting cells (APC) in vitro and in vivo. Antigen-pulsed APC [including macrophages, B cells and dendritic cells (DC)] were incubated or not with MPL, and their ability to sensitize naive T cells was tested in vitro and in vivo. The data show that MPL enhances the ability of macrophages and B cells to sensitize naive T cells, and confers to them the capacity to induce the development of T(h)1 and T(h)2. Administration of MPL i.v. in mice results in the redistribution of fully mature DC in the T cell area of the spleen. These observations suggest that MPL may induce an antigen-specific primary immune response by provoking the migration and maturation of DC that are the physiological adjuvant of the immune system.

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The monoclonal anti-idiotypic antibody (mAb2) 87.92.6 directed against the 9B.G5 antibody specific for the virus neutralizing epitope on the mammalian reovirus type 3 hemagglutinin was previously demonstrated to express an internal image of the receptor binding epitope of the reovirus type 3. Furthermore, this mAb2 has autoimmune reactivity to the cell surface receptor of the reovirus. The nucleotide and deduced amino acid sequences of the 87.92.6 mAb2 heavy and light chains are described in this report. The sequence analysis reveals that the same heavy chain variable and joining (VH and JH) gene segments are used by the 87.92.6 anti-idiotypic mAb2 and by the dominant idiotypes of the BALB/c anti-GAT (cGAT) and anti-NP (NP3) responses. [GAT; random polymer that is 60% glutamic acid, 30% alanine, and 10% tyrosine. NP; (4-hydroxy-3-nitrophenyl)-acetyl.] Despite extensive homology at the level of the heavy chain variable regions, the NP3 positive BALB/c anti-NP monoclonal antibody 17.2.25 binds neither 9B.G5 nor the cellular receptor for the hemagglutinin. Amino acid sequence comparison between the viral hemagglutinin and the 87.92.6 mAb2 light chain "internal image," reveals an area of significant homology indicating that antigen mimicry by antibodies may be achieved by sharing primary structure.

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