INVOLVEMENT OF THE VACUOLAR H+-ATPASE IN ANIMAL VIRUS ENTRY
INVOLVEMENT OF THE VACUOLAR H+-ATPASE IN ANIMAL VIRUS ENTRY
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DOI：
10.1099/0022-1317-75-10-2595
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发表时间：
1994-10-01
影响因子：
3.8
通讯作者：
CARRASCO, L
中科院分区：
文献类型：
--
作者：
PEREZ, L;CARRASCO, L
塞姆利基森林病毒（SFV）通过受体介导的内吞作用进入细胞，随后通过液泡H+-ATP酶的作用使内体酸化。病毒和内体膜的融合将病毒基因组递送到细胞质。如果在感染的最初几分钟内存在该化合物，则通过选择性抑制剂巴弗洛霉素A1（BFLA 1）直接阻断液泡H+-ATP酶可防止SFV感染细胞。病毒颗粒的附着和穿透不是抗生素的目标。BFLA 1和离子载体莫能菌素即使在低pH下也能有效地阻断SFV感染，表明酸性pH不足以使SFV将其基因组递送到细胞质，但H+-ATP酶泵的正常功能是必要的。其他含有包膜RNA的病毒，如水泡性口炎病毒或流感病毒也被BFLA 1阻断，而仙台病毒则没有观察到任何效果，仙台病毒通过与质膜直接融合进入细胞。包膜DNA含有病毒，如疱疹病毒和牛痘病毒，感染细胞，即使当液泡H+-ATP酶被BFLA 1抑制，观察到类似的行为与脊髓灰质炎病毒和腺病毒。动物病毒颗粒在进入过程中促进蛋白质和其他大分子的内化。BFLA 1阻断毒素α-八叠球菌素的共同进入时，诱导SFV，但不诱导仙台病毒。通过有效抑制剂BFLA 1抑制负责内体酸化的酶构成了分析病毒进入期间低pH依赖性机制的选择性和强大工具，并将有助于理解动物病毒进入细胞的机制和途径。
Semliki Forest virus (SFV) enters cells by receptor-mediated endocytosis, followed by acidification of endosomes by the action of the vacuolar H+-ATPase. Fusion of the viral and the endosomal membrane delivers the viral genome to the cytoplasm. Direct blockade of the vacuolar H+-ATPase by the selective inhibitor bafilomycin A1 (BFLA1) prevented the infection of cells by SFV, if the compound was present during the first minutes of infection. Attachment and penetration of virus particles were not the targets of the antibiotic. BFLA1 and the ionophore monensin potently blocked SFV infection even at low pH, indicating that acidic pH is not sufficient for SFV to deliver its genome to the cytoplasm, but the proper functioning of the H+-ATPase pump is necessary. Other enveloped RNA-containing viruses, such as vesicular stomatitis virus or influenza virus were also blocked by BFLA1, whereas no effect was observed with Sendai virus, which enters into cells by direct fusion with the plasma membrane. Enveloped DNA-containing viruses, such as herpesviruses and vaccinia virus, infected the cells even when the vacuolar H+-ATPase was inhibited by BFLA1; similar behaviour was observed with poliovirus and adenovirus. Animal virus particles promote the internalization of proteins and other macromolecules during entry. BFLA1 blocked co-entry of the toxin alpha-sarcin when induced by SFV, but not when induced by Sendai virus. The inhibition of the enzyme responsible for acidification of endosomes by means of the potent inhibitor BFLA1 constitutes a selective and powerful tool to analyse the low-pH dependent mechanism(s) during virus entry and will aid in understanding the mechanisms and routes of entry of animal viruses into cells.