Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, Laval, QC, H7V 1B7, Canada.
The McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
Nat Commun. 2023 Jun 14;14(1):3515. doi: 10.1038/s41467-023-38875-x.
Parvoviruses (family Parvoviridae) are currently defined by a linear monopartite ssDNA genome, T = 1 icosahedral capsids, and distinct structural (VP) and non-structural (NS) protein expression cassettes within their genome. We report the discovery of a parvovirus with a bipartite genome, Acheta domesticus segmented densovirus (AdSDV), isolated from house crickets (Acheta domesticus), in which it is pathogenic. We found that the AdSDV harbors its NS and VP cassettes on two separate genome segments. Its vp segment acquired a phospholipase A2-encoding gene, vpORF3, via inter-subfamily recombination, coding for a non-structural protein. We showed that the AdSDV evolved a highly complex transcription profile in response to its multipartite replication strategy compared to its monopartite ancestors. Our structural and molecular examinations revealed that the AdSDV packages one genome segment per particle. The cryo-EM structures of two empty- and one full-capsid population (3.3, 3.1 and 2.3 Å resolution) reveal a genome packaging mechanism, which involves an elongated C-terminal tail of the VP, "pinning" the ssDNA genome to the capsid interior at the twofold symmetry axis. This mechanism fundamentally differs from the capsid-DNA interactions previously seen in parvoviruses. This study provides new insights on the mechanism behind ssDNA genome segmentation and on the plasticity of parvovirus biology.
细小病毒（家族细小病毒科）目前的定义是具有线性单分子部分 ssDNA 基因组、T = 1 二十面体衣壳，以及其基因组内独特的结构（VP）和非结构（NS）蛋白表达盒。我们报告了一种具有二分体基因组的细小病毒的发现，即来自蟋蟀（Acheta domesticus）的蟋蟀分段浓核病毒（AdSDV），在蟋蟀中它是致病的。我们发现，AdSDV 的 NS 和 VP 盒位于两个单独的基因组片段上。它的 vp 片段通过亚科间重组获得了一个编码磷脂酶 A2 的基因 vpORF3，编码一个非结构蛋白。我们表明，与单分子部分祖先相比，AdSDV 进化出了一种高度复杂的转录谱，以应对其多分子复制策略。我们的结构和分子检查表明，AdSDV 每个颗粒包装一个基因组片段。两个空衣壳和一个满衣壳群体（3.3、3.1 和 2.3Å 分辨率）的冷冻电镜结构揭示了一种基因组包装机制，该机制涉及 VP 的 C 端长尾，“将 ssDNA 基因组固定”在衣壳内部的二倍对称轴上。这种机制与以前在细小病毒中看到的衣壳-DNA 相互作用有根本的不同。本研究为 ssDNA 基因组分段背后的机制以及细小病毒生物学的可塑性提供了新的见解。
