β3 integrins mediate the cellular entry of hantaviruses that cause respiratory failure
β3 integrins mediate the cellular entry of hantaviruses that cause respiratory failure
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DOI：
10.1073/pnas.95.12.7074
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发表时间：
1998-06-09
影响因子：
11.1
通讯作者：
Mackow, ER
中科院分区：
文献类型：
--
作者：
Gavrilovskaya, IN;Shepley, M;Mackow, ER
新出现的汉坦病毒主要在肺内皮细胞复制，导致急性血小板丢失，导致汉坦病毒肺综合征(HPS)。我们现在报道，在血小板和内皮细胞上表达的特定整合素允许HPS相关汉坦病毒进入细胞。HPS相关汉坦病毒NY-1和新诺布雷病毒(SNV)的感染可被β(3)整合素抗体和β(3)整合素配体Vitronectin抑制。相比之下，非致病性(无相关人类疾病)的展望山病毒的感染可被纤维连接蛋白和贝塔(1)特异性抗体抑制，但不能被贝塔(3)特异性抗体或玻璃体连结蛋白抑制。重组α(IIIb)β(3)或α(V)β(3)整合素使细胞对NY-1和SNV的感染呈阳性反应，但不能感染展望山病毒，表明α(IIb)β(3)和α(V)β(3)整合素介导了NY-land SNV汉坦病毒的入侵。此外，进入；是二价阳离子不依赖的，不被精氨酸-甘氨酸-天冬氨酸多肽阻断，并且仍然由配体结合缺陷的α(IIb)β(3)-整合素突变体介导。因此，NY-1。SNV进入不依赖于β(3)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。
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 beta(3) integrins and by the beta(3)-integrin ligand, vitronectin. In contrast, infection with the nonpathogenic (no associated human disease) Prospect Hill virus was inhibited by fibronectin and beta(1)-specific antibodies but not by beta(3)-specific antibodies or vitronectin. Transfection with recombinant alpha(IIIb)beta(3) or alpha(v) beta(3) integrins rendered cells permissive to NY-1 and SNV but not Prospect Hill virus infection, indicating that alpha(IIb)beta(3) and alpha(v) beta(3) integrins mediate the entry of NY-land SNV hantaviruses. Furthermore, entry;is divalent cation independent, not blocked by arginine-glycine-aspartic acid peptides and still mediated by, ligand-binding defective, alpha(IIb)beta(3)-integrin mutants. Hence, NY-1. and SNV entry is independent of beta(3) integrin binding to physiologic ligands. These findings implicate integrins as cellular receptors for hantaviruses and indicate that hantavirus pathogenicity correlates with integrin usage.