CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy

Zhang, Gang; Campbell, Grant R.; Zhang, Qiangzhe; Maule, Erin; Hanna, Jonathan; Gao, Weiwei; Zhang, Liangfang; Spector, Stephen A.

Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable. Here, we investigate the potential of nanoengineered CD4(+) T cell membrane-coated nanoparticles (TNP) to neutralize a broad range of HIV-1 strains. TNP displayed outstanding neutralizing breadth and potency; they neutralized all 125 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, and transmitted/founder viruses, with a geometric mean 80% inhibitory concentration (IC(80)) of 819 μg ml(−1) (range, 72 to 8,570 μg ml(−1)). TNP also selectively bound to and induced autophagy in HIV-1-infected CD4(+) T cells and macrophages, while having no effect on uninfected cells. This TNP-mediated autophagy inhibited viral release and reduced cell-associated HIV-1 in a dose- and phospholipase D1-dependent manner. Genetic or pharmacological inhibition of autophagy ablated this effect. Thus, we can use TNP as therapeutic agents to neutralize cell-free HIV-1 and to target HIV-1 gp120-expressing cells to decrease the HIV-1 reservoir.