The Salivary Secretome of the Tsetse Fly Glossina pallidipes (Diptera: Glossinidae) Infected by Salivary Gland Hypertrophy Virus

Tsetse fly (Diptera; Glossinidae) transmits two devastating diseases to farmers (human African Trypanosomiasis; HAT) and their livestock (Animal African Trypanosomiasis; AAT) in 37 sub-Saharan African countries. During the rainy seasons, vast areas of fertile, arable land remain uncultivated as farmers flee their homes due to the presence of tsetse. Available drugs against trypanosomiasis are ineffective and difficult to administer. Control of the tsetse vector by Sterile Insect Technique (SIT) has been effective. This method involves repeated release of sterilized males into wild tsetse populations, which compete with wild type males for females. Upon mating, there is no offspring, leading to reduction in tsetse populations and thus relief from trypanosomiasis. The SIT method requires large-scale tsetse rearing to produce sterile males. However, tsetse colony productivity is hampered by infections with the salivary gland hypertrophy virus, which is transmitted via saliva as flies take blood meals during membrane feeding and often leads to colony collapse. Here, we investigated the salivary gland secretome proteins of virus-infected tsetse to broaden our understanding of virus infection, transmission and pathology. By this approach, we obtain insight in tsetse-hytrosavirus interactions and identified potential candidate proteins as targets for developing biotechnological strategies to control viral infections in tsetse colonies

Viral product trafficking to mitochondria, mechanisms and roles in pathogenesis

A wide variety of viruses cause significant morbidity and mortality in humans. However, targeted antiviral therapies have been developed for only a subset of these viruses, with the majority of currently licensed antiviral drugs targeting viral entry, replication or exit steps during the viral life cycle. Due to increasing emergence of antiviral drug resistant viruses, the isolation of multiple viral subtypes, and toxicities of existing therapies, there remains an urgent need for the timely development of novel antiviral agents, including those targeting host factors essential for viral replication. This review summarizes viral mitochondrial products and their effects on common mitochondria regulated pathways. These viral products and the mitochondrial pathways affected by them provide potential novel targets for the rational design of antiviral drugs. Viral products alter oxidative balance, mitochondrial permeability transition pore, mitochondrial membrane potential, electron transport and energy production. Moreover, viruses may cause the Warburg Effect, in which metabolism is reprogrammed to aerobic glycolysis as the main source of energy. Finally, viral products affect proapoptotic and antiapoptotic signaling, as well as mitochondrial innate immune signaling. Because of their importance for the generation of metabolic intermediates and energy as well as cell survival, mitochondrial pathways are targeted by multiple independent viral products. Structural modifications of existing drugs targeted to mitochondrial pathways may lead to the development of novel antiviral drugs with improved efficacy and reduced toxicity

Differential and stage-related expression in embryonic tissues of a new human homoeobox gene

The homoeobox is a 183 base-pair (bp) DNA sequence conserved in several Drosophila genes controlling segmentation and segment identity. Homoeobox sequences have been detected in the genome of species ranging from insects and anellids to vertebrates and homoeobox containing genes have been cloned from Xenopus, mouse and man. We recently isolated human homoeobox containing complementary DNA clones, that represent transcripts from four different human genes. One clone (HHO.c10) is selectively expressed in a 2.1 kilobase (kb) polyadenylated transcript in the spinal cord of human embryos and fetuses 5-10 weeks after fertilization. We report the characterization of a second cDNA clone, termed HHO.c13, that represents a new homoeobox gene. This clone encodes a protein of 255 amino-acid residues, which includes a pentapeptide, upstream of the homoeo domain, conserved in other Drosophila, Xenopus, murine and human homoeobox genes. By Northern analysis HHO.c13 detects multiple embryonic transcripts, which are differentially expressed in spinal cord, brain, backbone rudiments, limb buds and heart in 5-9-week-old human embryos and fetuses, in a striking organ- and stage-specific pattern. These observations suggest that in early mammalian development homoeobox genes may exert a wide spectrum of control functions in a variety of organs and body parts, in addition to the spinal cord