A viral phospholipase A2 is required for parvovirus infectivity

A viral phospholipase A2 is required for parvovirus infectivity
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DOI:
10.1016/s1534-5807(01)00031-4
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发表时间:
2001-08-01
期刊:
影响因子:
11.8
通讯作者:
Tijssen, P
Tijssen, P
中科院分区:
生物学1区
文献类型:
--
作者:
Zádori, Z;Szelei, J;Tijssen, P

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序列分析表明,细小病毒衣壳蛋白中含有磷脂酶A(2)(PLA(2))基序。尽管还不知道病毒中存在PLA 2活性,但来自不同细小病毒、人B19、猪细小病毒和昆虫GmDNV的推定PLA(2关键氨基酸的突变强烈降低PLA(2)活性,并成比例地降低病毒感染性,但细胞表面附着,进入,而PLA(2)缺陷型病毒粒子的内吞作用不受影响。PLA(2)活性对于病毒基因组从晚期内体/溶酶体有效转移到细胞核以启动复制至关重要。这些发现为开发PLA(2)抑制剂作为一类新的抗细小病毒感染及相关疾病的抗病毒药物提供了前景。
Sequence analysis revealed phospholipase A(2) (PLA(2)) motifs in capsid proteins of parvoviruses. Although PLA2 activity is not known to exist in viruses, putative PLA(2)s from divergent parvoviruses, human B19, porcine parvovirus, and insect GmDNV (densovirus from Galleria mellonella), can emulate catalytic properties of secreted PLA(2-) Mutations of critical amino acids strongly reduce both PLA(2) activity and, proportionally, viral infectivity, but cell surface attachment, entry, and endocytosis by PLA(2)-deficient virions are not affected. PLA(2) activity is critical for efficient transfer of the viral genome from late endosomes/lysosomes to the nucleus to initiate replication. These findings offer the prospect of developing PLA(2) inhibitors as a new class of antiviral drugs against parvovirus infections and associated diseases.