Chtarbanova Stanislava, Lamiable Olivier, Lee Kwang-Zin, Galiana Delphine, Troxler Laurent, Meignin Carine, Hetru Charles, Hoffmann Jules A, Daeffler Laurent, Imler Jean-Luc
CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France Faculté des Sciences de la Vie, Université de Strasbourg, Strasbourg, France.
J Virol. 2014 Dec;88(24):14057-69. doi: 10.1128/JVI.02320-14. Epub 2014 Sep 24.
Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop.
DCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the tropism of the virus for an essential but poorly characterized organ in the digestive tract, the crop. Our results may have relevance for other members of the Dicistroviridae, some of which are pathogenic to beneficial or pest insect species.
果蝇C病毒（DCV）是一种正义RNA病毒，属于双顺反子病毒科。这种模式生物黑腹果蝇的天然病原体常用于研究果蝇的抗病毒宿主防御，其中涉及RNA干扰和诱导反应。尽管在这些研究中，致死率通常被用作抗病毒免疫反应效率的指标，但病毒在果蝇中引起的病理变化仍知之甚少。在此，我们描述了与系统性DCV感染相关的发病机制。对感染DCV或其他两种正义RNA病毒（禽舍病毒和辛德毕斯病毒）的果蝇转录组进行比较，结果显示，与其他两种病毒不同，DCV感染会抑制大量基因的表达。其中一些基因在中肠中特异性表达，并且也会因饥饿而受到抑制。我们发现，系统性DCV感染会引发果蝇的营养应激，这是由于中肠入口处围食膜的积累以及在嗉囊（一个盲端肌肉性食物储存器官）中摄入食物的积累导致肠道阻塞所致。相关病毒蟋蟀麻痹病毒（CrPV）能在果蝇中高效生长，但不会引发这种病理变化。我们发现，DCV而非CrPV感染嗉囊周围的平滑肌，导致广泛的细胞病变，并大幅降低收缩率。我们得出结论，与系统性DCV感染相关的发病机制是由于该病毒对双翅目昆虫前肠中的一个重要器官——嗉囊具有嗜性。
DCV是少数几种已确定的影响模式生物黑腹果蝇的天然病毒病原体之一。因此，它是一种重要的病毒，有助于解读昆虫宿主与病毒之间的相互作用。我们在此描述了与果蝇DCV感染相关的发病机制，并表明这是由于该病毒对消化道中一个重要但特征不明的器官——嗉囊具有嗜性所致。我们的研究结果可能与双顺反子病毒科的其他成员有关，其中一些成员对有益昆虫或害虫物种具有致病性。
