Mihaylov Ivailo S, Cotmore Susan F, Tattersall Peter
Department of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Department of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Virology. 2014 Nov;468-470:226-237. doi: 10.1016/j.virol.2014.07.043. Epub 2014 Sep 6.
Parvoviruses encode a small number of ancillary proteins that differ substantially between genera. Within the genus Protoparvovirus, minute virus of mice (MVM) encodes three isoforms of its ancillary protein NS2, while human bocavirus 1 (HBoV1), in the genus Bocaparvovirus, encodes an NP1 protein that is unrelated in primary sequence to MVM NS2. To search for functional overlap between NS2 and NP1, we generated murine A9 cell populations that inducibly express HBoV1 NP1. These were used to test whether NP1 expression could complement specific defects resulting from depletion of MVM NS2 isoforms. NP1 induction had little impact on cell viability or cell cycle progression in uninfected cells, and was unable to complement late defects in MVM virion production associated with low NS2 levels. However, NP1 did relocate to MVM replication centers, and supports both the normal expansion of these foci and overcomes the early paralysis of DNA replication in NS2-null infections.
细小病毒编码少量辅助蛋白,不同属之间的辅助蛋白差异很大。在细小病毒属中,小鼠微小病毒(MVM)编码其辅助蛋白NS2的三种异构体,而博卡细小病毒属中的人博卡病毒1型(HBoV1)编码一种NP1蛋白,其一级序列与MVM NS2无关。为了寻找NS2和NP1之间的功能重叠,我们构建了可诱导表达HBoV1 NP1的小鼠A9细胞群体。这些细胞用于测试NP1的表达是否可以弥补因MVM NS2异构体缺失而导致的特定缺陷。NP1的诱导对未感染细胞的细胞活力或细胞周期进程影响很小,并且无法弥补与低NS2水平相关的MVM病毒体产生的晚期缺陷。然而,NP1确实会重新定位到MVM复制中心,并支持这些病灶的正常扩展,同时克服NS2缺失感染中DNA复制的早期停滞。