Campbell Corey L, Torres-Perez Fernando, Acuna-Retamar Mariana, Schountz Tony
Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
Instituto de Biología, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.
PLoS One. 2015 Apr 9;10(4):e0122935. doi: 10.1371/journal.pone.0122935. eCollection 2015.
Long-tailed pygmy rice rats (Oligoryzomys longicaudatus) are principal reservoir hosts of Andes virus (ANDV) (Bunyaviridae), which causes most hantavirus cardiopulmonary syndrome cases in the Americas. To develop tools for the study of the ANDV-host interactions, we used RNA-Seq to generate a de novo transcriptome assembly. Splenic RNA from five rice rats captured in Chile, three of which were ANDV-infected, was used to generate an assembly of 66,173 annotated transcripts, including noncoding RNAs. Phylogenetic analysis of selected predicted proteins showed similarities to those of the North American deer mouse (Peromyscus maniculatus), the principal reservoir of Sin Nombre virus (SNV). One of the infected rice rats had about 50-fold more viral burden than the others, suggesting acute infection, whereas the remaining two had levels consistent with persistence. Differential expression analysis revealed distinct signatures among the infected rodents. The differences could be due to 1) variations in viral load, 2) dimorphic or reproductive differences in splenic homing of immune cells, or 3) factors of unknown etiology. In the two persistently infected rice rats, suppression of the JAK-STAT pathway at Stat5b and Ccnot1, elevation of Casp1, RIG-I pathway factors Ppp1cc and Mff, and increased FC receptor-like transcripts occurred. Caspase-1 and Stat5b activation pathways have been shown to stimulate T helper follicular cell (TFH) development in other species. These data are also consistent with reports suggestive of TFH stimulation in deer mice experimentally infected with hantaviruses. In the remaining acutely infected rice rat, the apoptotic pathway marker Cox6a1 was elevated, and putative anti-viral factors Abcb1a, Fam46c, Spp1, Rxra, Rxrb, Trmp2 and Trim58 were modulated. Transcripts for preproenkephalin (Prenk) were reduced, which may be predictive of an increased T cell activation threshold. Taken together, this transcriptome dataset will permit rigorous examination of rice rat-ANDV interactions and may lead to better understanding of virus ecology.
长尾侏儒稻鼠（Oligoryzomys longicaudatus）是安第斯病毒（ANDV，布尼亚病毒科）的主要储存宿主，该病毒导致了美洲大多数汉坦病毒心肺综合征病例。为了开发研究ANDV与宿主相互作用的工具，我们使用RNA测序来生成一个从头转录组组装。来自在智利捕获的五只稻鼠的脾脏RNA，其中三只感染了ANDV，用于生成一个包含66173个注释转录本的组装，包括非编码RNA。对选定预测蛋白的系统发育分析显示与北美鹿鼠（Peromyscus maniculatus）的蛋白相似，北美鹿鼠是辛诺柏病毒（SNV）的主要储存宿主。其中一只感染的稻鼠的病毒载量比其他稻鼠高约50倍，表明是急性感染，而其余两只的病毒载量水平与持续性感染一致。差异表达分析揭示了受感染啮齿动物之间的不同特征。这些差异可能是由于1）病毒载量的变化，2）免疫细胞在脾脏归巢中的二态性或生殖差异，或3）病因不明的因素。在两只持续感染的稻鼠中，Stat5b和Ccnot1处的JAK-STAT途径受到抑制，Casp1、RIG-I途径因子Ppp1cc和Mff升高，并且Fc受体样转录本增加。在其他物种中，已证明半胱天冬酶-1和Stat5b激活途径可刺激滤泡辅助性T细胞（TFH）的发育。这些数据也与关于实验感染汉坦病毒的鹿鼠中TFH受到刺激的报道一致。在其余急性感染的稻鼠中，凋亡途径标记物Cox6a1升高，并且推定的抗病毒因子Abcb1a、Fam46c、Spp1、Rxra、Rxrb、Trmp2和Trim58受到调节。前脑啡肽原（Prenk）的转录本减少，这可能预示着T细胞激活阈值升高。综上所述，这个转录组数据集将允许对稻鼠与ANDV的相互作用进行严格研究，并可能有助于更好地理解病毒生态学。
