Expert opinion on therapeutic targets
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Expert Opin. Ther. Targets · Aug 2002
ReviewThe role of DC-SIGN and DC-SIGNR in HIV and Ebola virus infection: can potential therapeutics block virus transmission and dissemination?
Sexual transmission of HIV requires that the virus crosses mucosal barriers and disseminates into lymphoid tissue, the major site of viral replication. To achieve this, HIV might engage DC-SIGN, a calcium dependent lectin that is expressed on mucosal dendritic cells (DCs), which binds avidly to HIV. DC-SIGN and other attachment factors are likely to account for the well-known ability of DCs to enhance infection of T cells by HIV. ⋯ DC-SIGN and a related molecule, termed DC-SIGNR, also enhance infection by Ebola virus. The expression of these lectins on early targets of Ebola virus infection, like liver endothelial cells and alveolar macrophages, suggests an important role for DC-SIGN and DC-SIGNR in the establishment of Ebola infection. This article reviews the interaction of DC-SIGN and DC-SIGNR with HIV and Ebola, discusses the mechanism of DC-SIGN-mediated viral transmission and examines how this process could be inhibited by potential therapeutics.
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Expert Opin. Ther. Targets · Aug 2002
ReviewAirway smooth muscle: new targets for asthma pharmacotherapy.
Asthma, a chronic disease increasing in prevalence worldwide, is characterised by reversible airway obstruction, airway inflammation and airway smooth muscle (ASM) cell hyperplasia. The traditional view of ASM in asthma, as a regulator of bronchomotor tone, is rapidly changing. ⋯ This review discusses the synthetic function of ASM cells, defined as the ability to secrete cytokines, chemokines and growth factors and express surface receptors that are important for cell adhesion and leukocyte activation. Finally, the efficacy of established asthma therapies in modifying the synthetic function of ASM cells are compared and novel targets for pharmacological intervention are discussed.