Impact of modification of envelope proteins on the mechanical properties of HIV virus-like particles.

Abstract

The mechanical interactions between virus-like particles and host cells may offer targets for new viral treatments and vaccines with modes of action that are independent of the immune system. The physical properties of structures involved govern the particle-cell interactions. While the mechanical properties of virions and mammalian cells have been widely studied, data on virus-like particles are limited. This study aimed to determine the mechanical and morphological properties of HIV-1 virus-like particles with different envelopes. Three HIV-like particles, i.e. Gagᴹ + gp150, Gagᴹ + gp140HA₂tr, and Gagᴹ + gp120HA₂, were produced by combining the same Gag protein shell with different trimeric glycoprotein envelopes. The particles' spring constant, breaking force, and dimensions were determined using atomic force microscopy, and the elastic modulus was quantified using finite element analysis. Spring constant, elastic modulus, and breaking force were higher for Gagᴹ + gp140HA₂tr and Gagᴹ + gp120HA₂ than for Gagᴹ + gp150. The particle height was smaller for Gagᴹ + gp120HA₂ than for Gagᴹ + gp150 and Gagᴹ + gp140HA₂tr. Possible mechanisms underlying the increase of the particles' stiffness and mechanical strength are the inclusion of the influenza virus HA transmembrane domain in the HIV Env protein, and the lower expression and packing density of Env in Gagᴹ + gp140HA₂tr and Gagᴹ + gp120HA₂ compared to Gagᴹ + gp150 found previously. Upon confirmation, the proposed mechanisms offer potential to tailor the mechanics of HIV virus-like particles and guide mechanical interactions between VLPs and host cells towards improving vaccines.