Acute lung injury (ALI) is a life-threatening condition in critically ill patients. Injury to the alveolar epithelium is a critical event in ALI, and accumulating evidence suggests that it is linked to proapoptotic Fas/FasL signals. Active soluble FasL (sFasL) is detectable in the bronchoalveolar lavage (BAL) fluid of patients with ALI, but the mechanisms controlling its bioactivity are unclear. We therefore investigated how the structure of sFasL influences cellular activation in human and mouse lungs and the role of oxidants and proteases in modifying sFasL activity. The sFasL in BAL fluid from patients with ALI was bioactive and present in high molecular weight multimers and aggregates. Oxidants generated from neutrophil myeloperoxidase in BAL fluid promoted aggregation of sFasL in vitro and in vivo. Oxidation increased the biological activity of sFasL at low concentrations but degraded sFasL at high concentrations. The amino-terminal extracellular stalk region of human sFasL was required to induce lung injury in mice, and proteolytic cleavage of the stalk region by MMP-7 reduced the bioactivity of sFasL in human cells in vitro. The sFasL recovered from the lungs of patients with ALI contained both oxidized methionine residues and the stalk region. These data provide what we believe to be new insights into the structural determinants of sFasL bioactivity in the lungs of patients with ALI.

h Crimean-Congo hemorrhagic fever, a severe hemorrhagic disease found throughout Africa, Europe, and Asia, is caused by the tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is a negative-sense single-stranded RNA (ssRNA) virus belonging to the Nairovirus genus of the Bunyaviridae family. Its genome of three single-stranded RNA segments is encapsidated by the nucleocapsid protein (CCHFV N) to form the ribonucleoprotein complex. This ribonucleoprotein complex is required during replication and transcription of the viral genomic RNA. Here, we present the crystal structures of the CCHFV N in two distinct forms, an oligomeric form comprised of double antiparallel superhelices and a monomeric form. The head-to-tail interaction of the stalk region of one CCHFV N subunit with the base of the globular body of the adjacent subunit stabilizes the helical organization of the oligomeric form of CCHFV N. It also masks the conserved caspase-3 cleavage site present at the tip of the stalk region from host cell caspase-3 interaction and cleavage. By incubation with primer-length ssRNAs, we also obtained the crystal structure of CCHFV N in its monomeric form, which is similar to a recently published structure. The conformational change of CCHFV N upon deoligomerization results in the exposure of the caspase-3 cleavage site and subjects CCHFV N to caspase-3 cleavage. Mutations of this cleavage site inhibit cleavage by caspase-3 and result in enhanced viral polymerase activity. Thus, cleavage of CCHFV N by host cell caspase-3 appears to be crucial for controlling viral RNA synthesis and represents an important host defense mechanism against CCHFV infection.

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Background Aedes albopictus, the Asian tiger mosquito, is an aggressive, highly anthropophilic, day-biting mosquito with an expanding geographic range. Suppression of Ae. albopictus is difficult because of the abundance and prevalence of larval habitats within peridomestic environments, particularly cryptic habitats such as corrugated extension spouts, fence post openings, discarded food containers, etc. Because of the challenges of eliminating or treating larval habitats of this species, we tested an autodissemination concept to contaminate these habitats with the insect growth regulator pyriproxyfen.MethodsOur study was conducted in the City of Trenton (Mercer County), New Jersey, USA (40°12′N, 74°44′W). We selected six hot spots, where five or more Ae. albopictus males or females were collected based on weekly trap surveillance. A trapping unit was a city block, approximately 0.8 ha (hot spot), where we deployed 26 to 28 autodissemination stations per treatment plot. To gauge efficacy, we deployed BGS traps, oviposition cups, and sentinel cups in treatment and control locations.ResultsWe found a significant reduction in eggs (P < 0.0001) and larval populations (P < 0.0001) as a result of treatment. Pupal mortality, as determined through bioassays, was also significantly higher in the treatment sites (P < 0.0001).ConclusionOur results clearly show the potential and unique use of the autodissemination stations to control immature Ae. albopictus in urban areas. Penetration of larvicides with existing methods are difficult to reach cryptic habitats, but the autodissemination approach, which exploits the oviposition behavior of the target pest, can be integrated into intervention programs. New tools are urgently needed to curb the expansion and public health implications of Ae. albopictus and other container-inhabiting species.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2034-7) contains supplementary material, which is available to authorized users.