人类免疫缺陷病毒1型(HIV-1)包膜糖蛋白(Env)在质膜(PM)上的颗粒组装位点掺入病毒体。Env到达组装和颗粒掺入位点所采取的路线仍未完全理解。在最初通过分泌途径递送到PM后,Env迅速内吞,这表明颗粒掺入需要回收。先前已证明以小GTP酶Rab14标记的内体在Env贩运中起作用。这里,我们研究了KIF16B的作用,指导依赖Rab14的货物向外运动的分子运动蛋白,在环境贩运中。Env在细胞外周与KIF16B+内体广泛共定位,而KIF16B的运动缺陷突变体的表达将Env重新分配到核周位置。在没有KIF16B的情况下,在细胞表面标记的Env的半衰期显着降低,而通过抑制溶酶体降解恢复正常的半衰期。在没有KIF16B的情况下,细胞表面的Env表达减少,导致Env掺入颗粒的减少和颗粒感染性的相应减少。与野生型细胞相比,KIF16B敲除细胞中的HIV-1复制大大减少。这些结果表明,KIF16B调节涉及Env贩运的向外分选步骤,从而限制溶酶体降解并增强颗粒掺入。重要性HIV-1包膜糖蛋白是HIV-1颗粒的必需成分。尚未完全了解有助于将包膜掺入颗粒中的细胞途径。这里,我们已经确定了KIF16B,一种运动蛋白,将运动从内部隔室引向质膜,作为防止包膜降解和增强颗粒掺入的宿主因子。这是鉴定出的第一个有助于HIV-1包膜掺入和复制的宿主运动蛋白。
The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) is incorporated into virions at the site of particle assembly on the plasma membrane (PM). The route taken by Env to reach the site of assembly and particle incorporation remains incompletely understood. Following initial delivery to the PM through the secretory pathway, Env is rapidly endocytosed, suggesting that recycling is required for particle incorporation. Endosomes marked by the small GTPase Rab14 have been previously shown to play a role in Env trafficking. Here, we examined the role of
KIF16B, the molecular motor protein that directs outward movement of Rab14-dependent cargo, in Env trafficking. Env colocalized extensively with KIF16B+ endosomes at the cellular periphery, while expression of a motor-deficient mutant of
KIF16B redistributed Env to a perinuclear location. The half-life of Env labeled at the cell surface was markedly reduced in the absence of
KIF16B, while a normal half-life was restored through inhibition of lysosomal degradation. In the absence of
KIF16B, Env expression on the surface of cells was reduced, leading to a reduction in Env incorporation into particles and a corresponding reduction in particle infectivity. HIV-1 replication in
KIF16B knockout cells was substantially reduced compared to that in wild-type cells. These results indicated that KIF16B regulates an outward sorting step involved in Env trafficking, thereby limiting lysosomal degradation and enhancing particle incorporation. IMPORTANCE The HIV-1 envelope glycoprotein is an essential component of HIV-1 particles. The cellular pathways that contribute to incorporation of envelope into particles are not fully understood. Here, we have identified KIF16B, a motor protein that directs movement from internal compartments toward the plasma membrane, as a host factor that prevents envelope degradation and enhances particle incorporation. This is the first host motor protein identified that contributes to HIV-1 envelope incorporation and replication.