The role of DC-SIGN and DC-SIGNR in HIV and Ebola virus infection: can potential therapeutics block virus transmission and dissemination?

Abstract

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. Attachment of HIV to DC-SIGN might thus enhance viral spread in mucosal tissues and, by taking advantage of the inherent capacity of DCs to migrate into lymphoid tissue, might promote viral dissemination within the host. 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.