Novel ‘lock-in and apoptosis’ strategy could help eliminate HIV reservoirs

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Researchers from Kumamoto University (Japan) have developed a compound that has been demonstrated to reduce viral budding in HIV-infected cells, inducing cell death via apoptosis. It is thought this strategy could contribute towards achieving complete eradication of viral reservoirs in the body.

HIV has been successfully suppressed via medication; however, the challenge is now to remove latent HIV reservoirs.

Removal of these dormant virus particles and eradication of HIV from the body are part of a shifting focus in this field. Viral reservoirs have previously been targeted via the ‘kick and kill’ approach developed several years ago, which uses a drug to target the reservoir cells and activate the virus allowing the immune system to take action. This strategy has shown promise in reverting and targeting latency, however, management of the infected cells after the ‘kick’ step is important, and as yet unsolved, in order to avoid these cells producing virions.

The novel approach pioneered at Kumamoto University has been termed ‘lock-in and apoptosis’. Using a newly synthesised compound, L-HIPPO, the researchers demonstrated that HIV protein Pr55Gag could be strongly bound and inhibited. They observed that this in turn interrupted the translocation of the virus from cytoplasm to plasma membrane, therefore supressing viral budding.

In addition, the team demonstrated that when L-HIPPO was administered to HIV-infected cells via a carrier (α-CDE) the virus became confined to the host cells, or ‘locked-in’, subsequently inducing cell death via the natural pathway of apoptosis.

The Japanese team hypothesize that this new strategy could bridge the gap between the ‘kick’ and ‘kill’ steps of the current eradication strategy in a promising step towards completely eradicating HIV from the body.

Author, Mikako Fujita (Kumamoto University), concluded: “Unfortunately, this approach is not immediately available for people infected with HIV. First, we have to improve upon the drugs that activate the virus and combine them with L-HIPPO to efficiently target the viral reservoir. This would be a big step towards a complete recovery from HIV. We believe that our research will help to completely eradicate AIDS.”

Sources: Tateishi H, Monde K, Anraki K, Koga R et al. A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”. Sci. Rep. 7 8957 (2017) (Epub); www.eurekalert.org/pub_releases/2017-10/ku-anm100217.php

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