The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

Dalgleish, Angus; Beverley, Peter C. L.; Clapham, Paul R.; Crawford, Dorothy H.; Greaves, Melvyn F.; Weiss, Robin A.

doi:10.1038/312763a0

Cited by 3,233 publications

(1,548 citation statements)

References 31 publications

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“…Although speculative, the function of VCBPs might be to recognize determinants on various pathogens. There is considerable precedent for IgSF-related viral receptors, including those for poliovirus (poliovirus receptor) 116 , reovirus (junctional adhesion molecule, JAM) 117 , HIV (CD4) 118 , mouse hepatitis virus (CEA-related cell-adhesion molecule 1, CEACAM1) 119 , measles virus (signalling lymphocytic activation molecule, SLAM) 120 and others. Other potential functions for VCBPs include binding to fungal or bacterial surfaces, direct opsonization, and self-and non-self-recognition 3,7 .…”

Section: Vcbps In Protochordatesmentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.The evolutionary development of the METAZOANS was associated with the diversification of a wide range of specialized cell-surface molecules that mediate key metabolic processes, as well as provide crucial contact interfaces and carry out a broad range of other essential functions. It is not unexpected that some of these molecules also came to function as barriers to pathogenic invasion and, in doing so, began to carry out dedicated innate immune protective functions. Whereas the simplest form of protection, barrier formation, is essentially mechanical in nature, relentless pressure from genetic variation in pathogens probably drove the evolution of such innate immune protective molecules towards diversification and, in parallel, towards integration of signalling pathways to regulate cellular responses to external stimulation. However, despite the sophistication that such innate immune mediators achieved over time, their biological complexity, by definition, would be limited by genome space, so with increasing complexity of body plan and/or increasing pathogen sophistication, they could be overwhelmed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMore than 500 million years ago, a TRANSPOSITION event, probably involving a recombinationactivating gene (RAG)-bearing element, might have given rise to the predecessors of the rearranging antigen-binding receptors of the jawed vertebrates, which encompass the vertebrate radiations that extend from the cartilaginous fish through to humans. This is considered the defining point in the emergence of RAG-mediated (conventional) adaptive immunity 1,2 , which has evolved to create a mechanism for deriving almost limitless variation from very few genes. Studies in traditional and non-traditional animal models, such as sharks, bony fish and birds, have brought this event and its ramifications for host defence into sharper focus. We can now predict much about how these rearranging antigenbinding receptors probably arose, what alternative pathways of immune-receptor gene evolution have occurred, what relationships exist between B-and T-cell-mediated immunity and natural killer (NK)-cell function, how complex immune ...

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Section: Vcbps In Protochordatesmentioning

confidence: 99%

Reconstructing immune phylogeny: new perspectives

2005

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“…The human immunode®ciency virus (HIV), the agent etiologically related to the acquired immunode®ciency syndrome (AIDS) (Barre-Sinoussi et al, 1983), preferentially infects helper inducer T lymphocytes (Dalgleish et al, 1984). Termination of the long latency of AIDS in patients infected with HIV-1 is marked by a profound depletion of CD4 + T cells and the decline of HIV-1 speci®c cytotoxic CD8 + T cells (Meyaard et al, 1992(Meyaard et al, ,1994.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Macho¹,

Calzado²,

Jiménez‐Reina³

et al. 1999

Oncogene

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The e ects of HIV-1 Tat protein on mitochondria membrane permeability and apoptosis were analysed in lymphoid cells. In this report we show that stabletransfected HIV-Tat cells are primed to undergo apoptosis upon serum withdrawal. This e ect was observed in both the Jhan T cell line and the K562 cells, the latter expressing the bcr-abl chimeric gene, which confers resistance to apoptosis induced by di erent stimuli. Using a cyto¯uorimetric approach we have determined that serum withdrawal induces a disruption of the transmembrane mitochondrial potential (Dc m ) followed by an increase of reactive oxygen species (ROS) and the subsequent DNA nuclear loss in K562-Tat cells but not in the K562-pcDNA cell line. These pre-apoptotic events were associated with the cleavage of the caspase-3, while the expression of Bcl-2, Bcl-X L and Bax proteins was not a ected by the presence of Tat. Regardless of the steady state of the Bax protein, we found that in both K562 and K562-Tat cells, this protein is located in the nucleus, but after serum withdrawal its localization was mainly in the cytoplasm. The activity of caspase-3 detected in K562-Tat cells after serum withdrawal paralleled with the mitochondria permeability transition. Nevertheless, in Jhan-Tat cells the inhibition of this caspase with the speci®c inhibitor, z-DEVD-cmk, did not a ect the disruption of the mitochondria potential induced by serum withdrawal. Interestingly, we found that HIV-Tat protein accumulates at the mitochondria in the K562-Tat cells cultured under low serum conditions, and this mitochondrial localization correlated with the Dc m disruption detected in these cells. In addition, HIV-1 Tat protein synergies with protoporphyrin IX (PPIX), a ligand of the mitochondrial benzodiazepine receptor, in the induction of apoptosis in both Jhan and K562 cells. Thus, HIV-1 Tat protein may induce apoptosis by a mechanism that involves mitochondrial PT and may contribute to the lymphocyte depletion seen in AIDS patients.

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“…Previous work from our laboratory has shown that oxidative stress produced by hydrogen peroxide can induce the reactivation of latent HIV-1 [20]. This virus predominantly infects T-helper cells, macrophages and monocytes [21]. Following penetration of these cells, its genome becomes integrated in cell chromosomes and the provirus can remain latent for several years.…”

Section: Introductionmentioning

confidence: 99%