Fasina Olufemi O, Stupps Stephanie, Figueroa-Cuilan Wanda, Pintel David J
Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, Missouri, USA.
Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, School of Medicine, Bond Life Sciences Center, Columbia, Missouri, USA
J Virol. 2017 May 26;91(12). doi: 10.1128/JVI.00260-17. Print 2017 Jun 15.
Parvoviruses use a variety of means to control the expression of their compact genomes. The bocaparvovirus minute virus of canines (MVC) encodes a small, genus-specific protein, NP1, which governs access to the viral capsid gene via its role in alternative polyadenylation and alternative splicing of the single MVC pre-mRNA. In addition to NP1, MVC encodes five additional nonstructural proteins (NS) that share an initiation codon at the left end of the genome and which are individually encoded by alternative multiply spliced mRNAs. We found that three of these proteins were encoded by mRNAs that excise the NP1-regulated MVC intron immediately upstream of the internal polyadenylation site, (pA)p, and that generation of these proteins was thus regulated by NP1. Splicing of their progenitor mRNAs joined the amino termini of these proteins to the NP1 open reading frame, and splice site mutations that prevented their expression inhibited virus replication in a host cell-dependent manner. Thus, in addition to controlling capsid gene access, NP1 also controls the expression of three of the five identified NS proteins via its role in governing MVC pre-mRNA splicing. The are small nonenveloped icosahedral viruses that are important pathogens in many animal species, including humans. Minute virus of canine (MVC) is an autonomous parvovirus in the genus It has a single promoter that generates a single pre-mRNA. NP1, a small genus-specific MVC protein, participates in the processing of this pre-mRNA and so controls capsid gene access via its role in alternative internal polyadenylation and splicing. We show that NP1 also controls the expression of three of the five identified NS proteins via its role in governing MVC pre-mRNA splicing. These NS proteins together are required for virus replication in a host cell-dependent manner.
细小病毒利用多种方式来控制其紧凑基因组的表达。犬博卡细小病毒（MVC）编码一种小的、属特异性蛋白NP1，它通过在单个MVC前体mRNA的可变聚腺苷酸化和可变剪接中发挥作用，来控制对病毒衣壳基因的访问。除了NP1，MVC还编码另外五种非结构蛋白（NS），它们在基因组左端共享一个起始密码子，并由可变多重剪接的mRNA分别编码。我们发现，其中三种蛋白由mRNA编码，这些mRNA切除了内部聚腺苷酸化位点（pA）p上游紧邻NP1调控的MVC内含子，因此这些蛋白的产生受NP1调控。它们的前体mRNA的剪接将这些蛋白的氨基末端与NP1开放阅读框连接起来，阻止其表达的剪接位点突变以宿主细胞依赖的方式抑制病毒复制。因此，除了控制衣壳基因的访问外，NP1还通过其在调控MVC前体mRNA剪接中的作用，控制已鉴定的五种NS蛋白中三种的表达。细小病毒是小型无包膜二十面体病毒，是包括人类在内的许多动物物种中的重要病原体。犬微小病毒（MVC）是该属中的一种自主细小病毒。它有一个单一启动子，产生一个单一的前体mRNA。NP1是一种小的属特异性MVC蛋白，参与该前体mRNA的加工，因此通过其在可变内部聚腺苷酸化和剪接中的作用来控制衣壳基因的访问。我们表明，NP1还通过其在调控MVC前体mRNA剪接中的作用，控制已鉴定的五种NS蛋白中三种的表达。这些NS蛋白共同以宿主细胞依赖的方式参与病毒复制。
