Gavrilovskaya I N, Shepley M, Shaw R, Ginsberg M H, Mackow E R
The Department of Medicine, Stony Brook University, HSC T17, Room 60, Stony Brook, NY 11794, USA.
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7074-9. doi: 10.1073/pnas.95.12.7074.
Newly emerged hantaviruses replicate primarily in the pulmonary endothelium, cause acute platelet loss, and result in hantavirus pulmonary syndrome (HPS). We now report that specific integrins expressed on platelets and endothelial cells permit the cellular entry of HPS-associated hantaviruses. Infection with HPS-associated hantaviruses, NY-1 and Sin Nombre virus (SNV), is inhibited by antibodies to beta3 integrins and by the beta3-integrin ligand, vitronectin. In contrast, infection with the nonpathogenic (no associated human disease) Prospect Hill virus was inhibited by fibronectin and beta1-specific antibodies but not by beta3-specific antibodies or vitronectin. Transfection with recombinant alphaIIb beta3 or alphav beta3 integrins rendered cells permissive to NY-1 and SNV but not Prospect Hill virus infection, indicating that alphaIIb beta3 and alphav beta3 integrins mediate the entry of NY-1 and SNV hantaviruses. Furthermore, entry is divalent cation independent, not blocked by arginine-glycine-aspartic acid peptides and still mediated by, ligand-binding defective, alphaIIb beta3-integrin mutants. Hence, NY-1 and SNV entry is independent of beta3 integrin binding to physiologic ligands. These findings implicate integrins as cellular receptors for hantaviruses and indicate that hantavirus pathogenicity correlates with integrin usage.
新出现的汉坦病毒主要在肺内皮细胞中复制，导致急性血小板减少，并引发汉坦病毒肺综合征（HPS）。我们现在报告，血小板和内皮细胞上表达的特定整合素允许与HPS相关的汉坦病毒进入细胞。针对β3整合素的抗体以及β3整合素配体玻连蛋白可抑制与HPS相关的汉坦病毒NY-1和辛诺柏病毒（SNV）的感染。相比之下，用纤连蛋白和β1特异性抗体可抑制非致病性（无相关人类疾病）的普罗斯佩克特山病毒的感染，但β3特异性抗体或玻连蛋白则无此作用。用重组αIIbβ3或αvβ3整合素转染细胞，使其对NY-1和SNV敏感，但对普罗斯佩克特山病毒感染不敏感，这表明αIIbβ3和αvβ3整合素介导NY-1和SNV汉坦病毒的进入。此外，病毒进入不依赖二价阳离子，不受精氨酸-甘氨酸-天冬氨酸肽的阻断，并且仍然可由配体结合缺陷的αIIbβ3整合素突变体介导。因此，NY-1和SNV的进入独立于β3整合素与生理配体的结合。这些发现表明整合素是汉坦病毒的细胞受体，并表明汉坦病毒的致病性与整合素的使用有关。
