Research ArticleHIV

An amphipathic peptide targeting the gp41 cytoplasmic tail kills HIV-1 virions and infected cells

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Science Translational Medicine  03 Jun 2020:
Vol. 12, Issue 546, eaaz2254
DOI: 10.1126/scitranslmed.aaz2254

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Making HIV its own worst enemy

Resistance to existing antivirals drives the need for identifying new ways to target HIV. Wang et al. screened a library of peptides from the HIV envelope protein to find ones that could inhibit the virus. One peptide, F9170, targeted HIV gp41 and was effective against free virions or HIV-infected cells. This peptide did not seem to be toxic or immunogenic in mice and is small enough to penetrate tissues that harbor HIV reservoirs. Simian-HIV–infected macaques treated with a short course of F9170 experienced a substantial drop in viral loads. Although further testing and development are needed, it could one day be part of a new treatment regimen for HIV.

Abstract

HIV-associated morbidity and mortality have markedly declined because of combinational antiretroviral therapy, but HIV readily mutates to develop drug resistance. Developing antivirals against previously undefined targets is essential to treat existing drug-resistant HIV strains. Some peptides derived from HIV-1 envelope glycoprotein (Env, gp120-gp41) have been shown to be effective in inhibiting HIV-1 infection. Therefore, we screened a peptide library from HIV-1 Env and identified a peptide from the cytoplasmic region, designated F9170, able to effectively inactivate HIV-1 virions and induce necrosis of HIV-1–infected cells, and reactivated latently infected cells. F9170 specifically targeted the conserved cytoplasmic tail of HIV-1 Env and effectively disrupted the integrity of the viral membrane. Short-term monoadministration of F9170 controlled viral loads to below the limit of detection in chronically SHIV-infected macaques. F9170 can enter the brain and lymph nodes, anatomic reservoirs for HIV latency. Therefore, F9170 shows promise as a drug candidate for HIV treatment.

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