Drosophila C Virus Systemic Infection Leads to Intestinal Obstruction

Abstract

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. IMPORTANCEDCV 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.

Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein

“…4C). Given that transcription is not repressed in CrPV-3(R146A)-infected cells, we propose that CrPV-1A is responsible for host transcriptional shutoff during infection, which is consistent with recent reports that dicistrovirus infection results in inhibition of transcription (48,64). A large body of research suggests that inhibition of transcription is beneficial for viruses (72)(73)(74).…”

“…CrPV infection modulates a number of cellular pathways, including host translation, transcriptional shutoff, and SG assembly (48,49,60,62,64). CrPV encodes at least 12 viral proteins, including 8 nonstructural and 4 structural proteins (61) (Fig.…”

Protection of Insects against Viral Infection by Apoptosis-Dependent Phagocytosis

“…We also noticed that DCV-infected adult flies showed retarded migration, but it is unclear whether this phenomenon has anything to do with fly mortality. Another report reasoned that a defect in the uptake of nutrients from the digestive tract is a direct cause of fly death postinfection of the intestine with DCV (62). It is necessary to clarify how infection with virus causes lethal damage in host organisms to develop an effective remedy to prevent and cure viral diseases.…”

“…Recent studies reported changes in the morphology of flies (i.e., abdominal swelling and crop enlargement) upon infection with DCV (31,62). We wondered whether such morphological changes are due to the expansion of infection.…”

“…However, it remains to be determined how flies succumb to DCV infection. DCV infects a variety of tissues and organs in Drosophila, including the fat body, periovarial sheath, trachea, muscle, and digestive tract (31,44,62,67,68). A recent report argued that alteration in a variety of physiological and metabolic phenomena is related to the death of DCV-infected flies (69).…”