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HIV: Banana lectin blocks infection

Condoms, when used consistently and correctly, prevent the spread of HIV. However, in developing countries – where the risk and consequences of infection are greatest – condom use is often restricted by cultural attitudes. The development of an effective anti-HIV microbicide could bypass this problem and prevent millions of new infections. An attractive target step for a microbicide is viral entry, and potential inhibitors include lectins that bind to viral surface glycans. David Markovitz and colleagues now identify a promising new candidate lectin, isolated from bananas, which binds to sugars on the HIV-1 envelope protein gp120. They report in the Journal of Biological Chemistry that the lectin, BanLec, potently blocks HIV-1 cellular entry and could form part of a preventative microbicide.

HIV-1 indicator cell lines express reporter genes under the control of a HIV promoter, and are a useful tool to rapidly assay for infection. The authors treated two such lines with nanomolar concentrations of BanLec and exposed them to HIV-1 isolated from several different sources. BanLec potently inhibited infection in a dose-dependent manner, irrespective of the viral subtype or tropism (host receptor preference). The lectin also inhibited replication of the virus in primary cells, as assayed using an ELISA for a viral protein.

Knowing that a compound prevents infection by, or replication of, HIV does not indicate which stage of infection is blocked. To investigate this, the authors used real-time PCR to detect the earliest HIV-1 reverse transcription product. The results showed that inhibition by BanLec occurs before viral replication begins. Suspecting that this known mannose-binding lectin might bind to the high-mannose glycosylations of the HIV-1 envelope protein gp120, the authors prepared an ELISA and confirmed their hypothesis. Furthermore, binding of an antibody that recognizes N-linked high-mannose structures at three gp120 sites was blocked by BanLec treatment.

Viral attachment and fusion, two independent steps that occur before replication, can be investigated separately with the use of temperature restriction. BanLec potently inhibited HIV attachment at concentrations that compared well with clinically approved anti-virals, and had a more modest effect on viral fusion.

This study adds BanLec to a group of lectins that are promising inhibitors of HIV infection. Clinical testing is needed to assess their toxicity, but the more components that can be included in a future lectin-based microbicide, the more likely it is to be effective, and the less likely it is that the virus could develop resistance. Moreover, glycosylations shield HIV from the host immune response so any alterations that prevent binding by lectins could expose the virus to neutralizing antibody responses. This killer's sweet disguise may yet be foiled.

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Author: Emma Leah