Means John C, Passarelli A Lorena
Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506-4901, USA.
Proc Natl Acad Sci U S A. 2010 May 25;107(21):9825-30. doi: 10.1073/pnas.0913582107. Epub 2010 May 10.
Most arthropod-borne and invertebrate viruses are orally ingested and commence infection in cells of the invertebrate intestine. Infection of secondary sites and eventual transmission to other hosts is hindered by basal lamina, a tightly interwoven and virus-impenetrable noncellular layer, lining the intestine and other organ cell layers. The mechanisms for viral escape across basal laminae are unknown. We describe an elegant mechanism mediated by a baculovirus-encoded fibroblast growth factor (vFGF) that signals a previously undescribed stepwise cascade of protease activation wherein matrix metalloproteases activate effector caspases, leading to remodeling of basal lamina lining tracheal cells associated with the intestine and culminating in the establishment of efficient systemic infections. Because FGFs coordinate diverse functions during development, metabolic processes, and tissue repair, it is plausible that the vFGF-mediated pathway described here is widely used during developmental and pathogenic processes that involve basal lamina remodeling.
大多数节肢动物传播的病毒和无脊椎动物病毒是通过口腔摄入,并在无脊椎动物肠道的细胞中开始感染。肠道和其他器官细胞层内衬有一层紧密交织且病毒无法穿透的非细胞层——基膜,这阻碍了病毒对次级部位的感染以及最终向其他宿主的传播。病毒穿过基膜的逃逸机制尚不清楚。我们描述了一种由杆状病毒编码的成纤维细胞生长因子(vFGF)介导的精妙机制,该机制引发了一个此前未被描述的蛋白酶激活的逐步级联反应,其中基质金属蛋白酶激活效应半胱天冬酶,导致与肠道相关的气管细胞内衬基膜重塑,并最终建立高效的全身感染。由于成纤维细胞生长因子在发育、代谢过程和组织修复中协调多种功能,因此这里描述的vFGF介导的途径很可能在涉及基膜重塑的发育和致病过程中被广泛使用。