Ascoviruses (family Ascoviridae) are double-stranded DNA viruses with circular genomes that attack lepidopterans, where they produce large, enveloped virions, 150 by 400 nm, and cause a chronic, fatal disease with a cytopathology resembling that of apoptosis. After infection, host cell DNA is degraded, the nucleus fragments, and the cell then cleaves into large virion-containing vesicles. These vesicles and virions circulate in the hemolymph, where they are acquired by parasitic wasps during oviposition and subsequently transmitted to new hosts. To develop a better understanding of ascovirus biology, we sequenced the genome of the type species Spodoptera frugiperda ascovirus 1a (SfAV-1a). The genome consisted of 156,922 bp, with a G؉C ratio of 49.2%, and contained 123 putative open reading frames coding for a variety of enzymes and virion structural proteins, of which tentative functions were assigned to 44. Among the most interesting enzymes, due to their potential role in apoptosis and viral vesicle formation, were a caspase, a cathepsin B, several kinases, E3 ubiquitin ligases, and especially several enzymes involved in lipid metabolism, including a fatty acid elongase, a sphingomyelinase, a phosphate acyltransferase, and a patatin-like phospholipase. Comparison of SfAV-1a proteins with those of other viruses showed that 10% were orthologs of Chilo iridescent virus proteins, the highest correspondence with any virus, providing further evidence that ascoviruses evolved from a lepidopteran iridovirus. The SfAV-1a genome sequence will facilitate the determination of how ascoviruses manipulate apoptosis to generate the novel virion-containing vesicles characteristic of these viruses and enable study of their origin and evolution.The family Ascoviridae was erected recently to accommodate several new species of large double-stranded DNA (dsDNA) viruses with circular genomes that attack insects of the order Lepidoptera at the larval and pupal stages, causing a chronic, fatal disease (38). Viruses of this family are characterized by large, enveloped virions with a distinctive reticulate surface pattern. Depending on the species, virions are either bacilliform or allantoid (sausage shaped), contain an internal lipid membrane surrounding the DNA/protein core, and are composed of at least 12 structural proteins, ranging in mass from 10 to 200 kDa (40).These structural characteristics of the virions are sufficient to distinguish ascoviruses from all other large dsDNA viruses. However, the most novel feature of ascoviruses is not their virion structure, but rather their unusual cellular pathology and transmission. Unlike for all other viruses, a variety of evidence suggests that ascoviruses induce apoptosis as part of a mechanism that enhances their reproduction and transmission. 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 memb...

The bone marrow (BM) niche impacts the progression of acute myeloid leukemia (AML) by favoring the chemoresistance of AML cells. Intimate interactions between leukemic cells and BM mesenchymal stromal cells (BM-MSCs) play key roles in this process. Direct intercellular communications between hematopoietic cells and BM-MSCs involve connexins, components of gap junctions. We postulated that blocking gap junction assembly could modify cell-cell interactions in the leukemic niche and consequently the chemoresistance. The comparison of BM-MSCs from AML patients and healthy donors revealed a specific profile of connexins in BM-MSCs of the leukemic niche and the effects of carbenoxolone (CBX), a gap junction disruptor, were evaluated on AML cells. CBX presents an antileukemic effect without affecting normal BM-CD34 + progenitor cells. The proapoptotic effect of CBX on AML cells is in line with the extinction of energy metabolism. CBX acts synergistically with cytarabine (Ara-C) in vitro and in vivo. Coculture experiments of AML cells with BM-MSCs revealed that CBX neutralizes the protective effect of the niche against the Ara-C-induced apoptosis of leukemic cells. Altogether, these results suggest that CBX could be of therapeutic interest to reduce the chemoresistance favored by the leukemic niche, by targeting gap junctions, without affecting normal hematopoiesis.

Mariner-like elements (MLE) are Class II transposable elements that are very widespread among eukaryotic genomes. One MLE belonging to the mauritiana subfamily, named Botmar1, has been identified in the genome of the bumble bee, Bombus terrestris. gDNA hybridization with the Botmar1 transposase ORF revealed that about 230 elements are present in each haploid genome of B. terrestris that consist entirely of 1.3- and 0.85-kbp elements. The analysis of their sequences revealed that there are two Botmar1 subfamilies of similar ages in the Bombus terrestris genome: one is composed entirely of 1.3-kpb elements, whereas the second comprises both completed and deleted elements. Our previous data indicated that the internally deleted form, which correspond to the 0.85-kbp Botmar1-related elements occur in other distantly related hymenopteran genomes. Because the presence of similar 1.3- and 0.85-kbp Botmar1-related elements in some distantly related hymenopteran species cannot be explained by horizontal transfers, the nucleic acid sequence properties of these elements were further investigated. We found that certain structural properties in their nucleic acid sequence might explain the occurrence of 0.85-kbp Botmar1-related elements presenting similarly located internal deletions in hymenopteran genomes.