Engineered Human Fusion Protein Stops HIV-1 Replication in Mice

(GENEVA) – Inspired by New World owl monkeys’ ability to make a fusion protein that potently blocks HIV-1 infection, scientists at the University of Geneva in Switzerland have engineered a human HIV-1 inhibitor.

Lead researcher Jeremy Luban points out that owl monkeys make AoT5Cyp, and that the human genome encodes the equivalent of the two components of this fusion protein, namely TRIM5 and cyclophilin A.

However, adds the researcher, humans do not make the T5Cyp fusion protein.

In their new study, Luban and colleagues have engineered a human HIV-1 inhibitor modeled after AoT5Cyp, by fusing human cyclophilin A to human TRIM5 (hT5Cyp).

The researchers said that the human fusion protein blocked HIV-1 infection of human macrophage and T cell lines, without disrupting normal cell function.

During the study, the researchers engineered some mice to lack B, T, and NK immune cells, so that the animals would not reject grafts of human material.

The team then engrafted with human CD4+ T cells engineered to contain hT5Cyp. HIV-1 replication was potently inhibited in these animals.

Based on their findings, the researchers came to the conclusion that hT5Cyp is a robust inhibitor of HIV-1 replication, and a promising anti-HIV-1 gene therapy candidate.

The study has been published in the Journal of Clinical Investigation.

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