A viral caspase contributes to modified apoptosis for virus transmission

Abstract

The Spodoptera frugiperda ascovirus, a DNA virus that attacks lepidopterans, codes for an executioner caspase synthesized by 9 h after infection of Sf21 cells. This caspase alone induces apoptosis in insect cells and, during viral replication in vivo, contributes to a novel cell cleavage process in which developing apoptotic bodies are rescued by the virus and differentiate to form large vesicles in which virions assemble. These viral vesicles disseminate to the blood, where they are acquired during egg-laying by parasitic wasps that transmit the virus. No other viruses encode caspases or form such modified apoptotic bodies, suggesting this caspase plays a direct role in cell partitioning that facilitates viral reproduction and transmission.Supplemental material is available at http://www.genesdev.org. Ascoviruses are complex double-stranded DNA viruses that attack lepidopterans, most commonly species of the family Noctuidae. Virions of these viruses are enveloped, bacilliform to allantoid in shape and 400 nm in length, and contain circular genomes, which, depending on the species, range from 116 to 180 kbp (Federici et al. 2000). An unusual feature of ascoviruses in comparison to most other viruses that attack invertebrates is that they are poorly infectious per os . Instead, laboratory experiments and ecological studies have shown that these viruses are transmitted mechanically by female parasitic wasps during oviposition. The ovipositor of the female wasp becomes contaminated with virions and virion-containing vesicles when inserted into an infected host to lay eggs. Subsequent oviposition in other caterpillars transfers virions to new hosts, resulting in their infection and death as well as the death of wasp progeny (Hamm et al. 1985;Govindarajan and Federici 1990;Tillman et al. 2004). An interesting exception to this transmission pattern is the ascovirus that attacks pupae of the leak moth, Acrolepiosis assectella. The genome of this ascovirus is carried unintegrated in the nuclei of males and females of its wasp vector, Diadromus pulchellus, and virions are transmitted vertically during oviposition by the wasp, which is highly dependent on this virus for parasitic success (Bigot et al. 1997).While the transmission of ascoviruses is unusual for an insect virus, the most novel feature of these viruses compared with all others is their reproductive cellular biology. After infecting a cell, these viruses initiate a cytopathology that resembles apoptosis, but in vivo differs significantly in several features. Within a few hours of infection, the nuclear membrane invaginates and then fragments (Federici 1983;Federici and Govindarajan 1990). Subsequently, rather than shrink and form characteristic apoptotic bodies by blebbing as cell death proceeds, the cell hypertrophies, enlarging as much as 10 times the size of healthy cells . As the cell enlarges, the plasma membrane invaginates as part of process that cleaves the cell into numerous virion-containing vesicles, 5-10 µm in diameter, which subsequently disperse ...

Genomic Sequence of Spodoptera frugiperda Ascovirus 1a , an Enveloped, Double-Stranded DNA Insect Virus That Manipulates Apoptosis for Viral Reproduction

“…This suggested that SfAV encoded proteins unique to this virus type that induce apoptosis and rescue the developing apoptotic bodies. As noted above, we demonstrated recently that SfAV encodes a functional executioner caspase (ORF 73) that apparently plays a direct role in initiating apoptosis (16). As executioner caspases also are known to be involved in the maturation of viral proteins (13), the SfAV caspase may also be involved in virion maturation.…”

“…A typical pattern of cytopathology, as exemplified by Spodoptera frugiperda ascovirus 1a (SfAV-1a), the type species, begins with nuclear hypertrophy and cleavage of host DNA, followed by lysis of the nucleus and fragmentation of the nuclear membrane. Recent studies demonstrating that SfAV-1a synthesizes an executioner caspase provide evidence that this virus plays a direct role in initiating apoptosis (16). After nuclear lysis, cellular hypertrophy ensues and what appear to be destined to become apoptotic bodies begin to form at the cell periphery by membrane invagination.…”

Flock House Virus Induces Apoptosis by Depletion of Drosophila Inhibitor-of-Apoptosis Protein DIAP1

“…Metallothionein promoter-directed gene expression was induced by overlaying stably transfected cells with supplemented Schneider's medium containing 500 M CuSO 4 . Where indicated below, infections were conducted in medium containing CuSO 4 .…”

“…FHV induces morphological defects during infection and is disseminated throughout the insect to diverse tissues, including the fat body, the midgut, muscle, and the head (9,19). These observations raise the interesting possibility that apoptosis facilitates FHV cell-to-cell spread, perhaps by the transport of FHV through apoptotic vesicles in a manner analogous to that of the invertebrate ascoviruses (4). Further studies of nodavirus infections in flies and mosquitoes should provide important insight into the role of apoptosis in viral pathology and virus spread in insects that vector medically relevant diseases in humans.…”

Proteomic analysis of the Spodoptera frugiperda ascovirus 1a virion reveals 21 proteins

“…In susceptible hosts, ascovirus pathology includes stunted larval growth and prolonged development and a novel cytopathology characterized by a modified form of virusinduced programmed cell death, in which apoptotic bodies are rescued as they develop and are converted into virioncontaining vesicles. After cleavage from the cell, these dissociate and accumulate in the haemolymph, changing its colour from translucent green to opaque white (Bideshi et al, 2005;Federici, 1983;Federici et al, 2005).…”