Carbohydrates on Hiv: Mediators of Immune Evasion and Targets for Antiviral Intervention

Abstract

Evaluation of: Pollicita M, Schols D, Aquaro S et al.: Carbohydrate-binding agents (CBAs) inhibit HIV-1 infection in human primary monocyte-derived macrophages (MDMs) and efficiently prevent MDM-directed viral capture and subsequent transmission to CD4 + T lymphocytes. Virology 370, 382–391 (2008). The heavily glycosylated HIV envelope protein (Env) facilitates infectious viral entry into cells. Oligosaccharides shield Env from the humoral immune response and facilitate binding to cellular lectins, such as DC-SIGN and mannose receptor (MR). Env glycans are also recognized by lectins isolated from plants and bacteria and by the carbohydrate-specific antibody 2G12. These agents potently inhibit viral infectivity, suggesting that the glycan shield of HIV is not only a major means of immune evasion but also a key target for antiviral intervention. Pollicita et al. demonstrate that lectins known to inhibit HIV-1 infection of T cells also suppress viral spread in macrophages. This finding is important, considering that macrophages are major HIV target cells and that Env proteins produced in macrophages and T cells differ substantially in glycosylation and lectin reactivity. Attachment of CXCR4-tropic HIV-1 to macrophages was mediated exclusively by MR and bound viruses were infectious for T cells in the absence of productive macrophage infection. Attachment and transinfection of T cells were blocked by lectins, indicating that carbohydrate-specific agents are suitable to inhibit both viral spread in macrophages and transmission of bound viruses to susceptible T cells. In summary, these observations demonstrate that inhibitors targeting Env glycans can be effective independent of the cellular source of the virus and thus have the potential to potently suppress viral spread in patients.