Editors' ChoiceHIV

HIV Gets a Wake-Up Call

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Science Translational Medicine  11 May 2011:
Vol. 3, Issue 82, pp. 82ec70
DOI: 10.1126/scitranslmed.3002598

In the game of hide-and-seek, an alert is called out to let all of the players know that the game has ended and they can come out of their hiding places. HIV is highly skilled at this game because even though highly active antiretroviral therapy (HAART) can suppress HIV replication, it is unable to eliminate the latent virus that continues to hide out in resting CD4+ T cells. HIV patients must take HAART for life because as soon as the treatment is stopped, the latent virus starts to replicate. Kovochich et al. now harness the power of nanotechnology to enhance the identification and removal of this well-hidden pathogen.

A number of HIV latency activators have been identified that activate resting T cells containing latent virus, resulting in production of HIV virions and concomitant activation of the host immune response. Kovochich et al. prepared multifunctional lipid nanoparticles (liposomes) and loaded them with the HIV latency activator bryostatin-2, a protein kinase C activator that stimulates resting T cells and induces latent HIV to replicate. They next incorporated a second drug—the protease inhibitor nelfinavir—into these lipid nanoparticles to simultaneously prevent the spread of the replicating virus. Lastly, the researchers attached an antibody to CD4 to their drug-loaded nanoparticles to promote targeted delivery of the liposomes to T cells.

Liposomes containing bryostatin-2 activated HIV in cultured CD4+ T cells and in T cells from a humanized mouse model. The addition of nelfinavir to the liposomes inhibited the spread of the activated, replicating virus in cultured T cells. Compared with a control liposome formulation that was not specifically targeted to CD4+ T cells, the antibody-directed bryostatin-2 liposomes preferentially bound to cultured CD4+ cells and activated latent HIV. Targeting a HIV latency activator encapsulated in liposomes to resting T cells infected with latent HIV is a clever therapeutic strategy that may signal the end of HIV’s game of hide-and-seek.

M. Kovochich et al., Activation of latent HIV using drug-loaded nanoparticles. PloS One 6, e18270 (2011). [PubMed]

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