Kobayashi Shintaro, Kawai Seira, Fukuda Yukine, Eguchi Haruto, Maezono Keisuke, Thammahakin Passawat, Sawa Hirofumi, Kariwa Hiroaki
Laboratory of Public Health, Faculty of Veterinary medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
Hokkaido University, Institute for Vaccine Research and Development (HU-IVReD), Sapporo, Hokkaido 001-0021, Japan.
iScience. 2024 Mar 19;27(4):109539. doi: 10.1016/j.isci.2024.109539. eCollection 2024 Apr 19.
Rab27a, a Rab family small GTPases, plays an important role in the trafficking and secretion of the intracellular proteins and has been reported to promote various viral multiplication. However, whether Rab27a is involved in West Nile virus (WNV) multiplication is unknown. This study examined the ability of Rab27a to suppress WNV multiplication. The inhibition of Rab27a expression increased viral multiplication and the intracellular levels of WNV structural proteins, E and prM proteins. Rab27a partially colocalized with E protein, mainly in the perinuclear region, while inhibition of Rab27a expression resulted in diffuse subcellular localization of E protein. In addition, some of the perinuclear E protein colocalized with the lysosomal marker LAMP1, and inhibition of lysosomal acidification increased intracellular levels of Rab27a and E proteins. These observations suggested that Rab27a inhibits WNV multiplication by inducing the degradation of viral protein in lysosomes.
Rab27a是一种Rab家族的小GTP酶，在细胞内蛋白质的运输和分泌中发挥重要作用，并且据报道可促进多种病毒的增殖。然而，Rab27a是否参与西尼罗河病毒（WNV）的增殖尚不清楚。本研究检测了Rab27a抑制WNV增殖的能力。Rab27a表达的抑制增加了病毒增殖以及WNV结构蛋白、E蛋白和prM蛋白的细胞内水平。Rab27a与E蛋白部分共定位，主要在核周区域，而Rab27a表达的抑制导致E蛋白在细胞内的定位弥散。此外，一些核周E蛋白与溶酶体标记物LAMP1共定位，溶酶体酸化的抑制增加了Rab27a和E蛋白的细胞内水平。这些观察结果表明，Rab27a通过诱导病毒蛋白在溶酶体中的降解来抑制WNV增殖。
