关键词： 传染病   疾病贮主   免疫系统   翼手目   人类  

摘要： 蝙蝠是百余种病毒的天然宿主,但它们并不会因此而染病,其原因何在?一项新研究发现,这或许与蝙蝠独特的"全天候"免疫系统有关.这一特性未来有可能为人类所用,以更好地保护人类健康. 有研究显示,蝙蝠这种飞行哺乳动物很可能是多种病毒在自然界的最初宿主.其中就包括近年来在全球多地引发疫情的"非典"病毒、中东呼吸综合征病毒、埃博拉病毒等,但蝙蝠自身却从没有受到这些病毒影响.

摘要： Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats.

摘要： Background. In our recent phase I immunotherapy (IT) trial in 23 women with metastatic breast cancer (MBC), 8 infusions of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) given in combination with interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) induced specific anti-breast cancer immunity. This study investigated whether specific cellular and humoral anti-breast cancer immunity induced by infusions of HER2 bispecific antibody armed T cells (BATs) could be transferred after high dose chemotherapy (HDC) and stem cell transplant (SCT) in MBC patients. Methods. T cell were activated with OKT3 and expanded in IL-2. ATC were harvested, armed with HER2Bi, and cryopreserved in 8 doses for twice weekly infusions for 4 weeks along with IL-2 and GM-CSF. Seven to 14 days after the last infusion of BATs, the patient was leukapheresed again to obtain and expand immune T cells. Multiple infusions of immune ATC after the HDC and SCT were given to boost the transferred cellular and humoral immune responses which were monitored up to 24 months. Results. Six of 8 MBC patients enrolled were evaluable in the protocol, no dose-limiting toxicity, delays in engraftment, or life-threatening infections were observed. Five of 6 evaluable patients exhibited increased anti- breast cancer cytotoxicity and IFN-γ Elispots after vaccination with BATs and up to 18 months post SCT. Serum and culture supernatants from in vitro antibody synthesis assay showed gradual increases in anti-SK-BR-3 IgG levels after SCT. Serum cytokine profile showed increases in IL-12 and Th1 cytokines. One out of 6 evaluable patients who rapidly progressed showed poor immune response, had high serum levels of Th2 cytokines and no evidence of transfer of immunity. Flow cytometry analysis of Vβ repertoire pattern in PBMC collected post IT and post SCT indicate transfer of the major Vβ clones post SCT that produced IFN-γ upon stimulation with breast cancer

关键词： 流感病毒   H17N10   H18N11   公共卫生   蝙蝠  

摘要： 甲型流感病毒能感染多种宿主。最近,在蝙蝠中鉴定出流感病毒两种新亚型:H17N10和H18N11,扩大了流感病毒宿主范围。与已知毒株不同的是,这两种蝙蝠病毒有着独特的复制特性。进化分析表明,这两种病毒在蝙蝠中长期独立进化,血清学检测阳性率极高。蝙蝠占已分类哺乳动物的20%,暗示有大量未定型的甲型流感病毒存在于这些庞大的隐形宿主中,其潜在流行可能性凸显了这些新病毒的公共卫生学意义。

关键词： NIPAH virus   ZOONOSES   DATE palm   FOOD consumption   HOMOLOGY (Biology)   ENZYME-linked immunosorbent assay   EPIDEMICS   POLYMERASE chain reaction  

关键词： Dengue virus   bats   dengue sylvatic cycle   Mexico  

摘要： Bats are reservoirs for viruses with zoonotic potential in the Americas, and scattered evidence exists suggesting that bats may act as reservoirs for dengue virus (DENV). To explore further the role of bats as part of DENV sylvatic cycles, 240 bats of 18 species were captured in 2 states of Mexico with contrasting ecological characteristics but concurrent DENV activity in humans. RT-PCR analysis of RNA extracted from liver or spleen tissue from de bats failed to show evidence for the presence of DENV nucleic acids in these organs. In addition, plasma assayed by plaque reduction neutralization test showed no evidence of neutralizing anti-DENV antibodies. These results suggest that American bats may not be reservoirs or amplification host for DENV infection.

关键词： VIRAL proteins   BAT diseases   VIRAL replication   ZOONOSES   DNA viruses   GUANO  

关键词： Bats   Microchiroptera   Monoclonal antibody   Immunoglobulins   B lymphocytes  

摘要： Bat immunity has received increasing attention because some bat species are being decimated by the fungal disease, White Nose Syndrome, while other species are potential reservoirs of zoonotic viruses. Identifying specific immune processes requires new specific tools and reagents. In this study, we describe a new mouse monoclonal antibody (mAb) reactive with Eptesicus fuscus immunoglobulins. The epitope recognized by mAb BT1-4F10 was localized to immunoglobulin light (lambda) chains;hence, the mAb recognized serum immunoglobulins and B lymphocytes. The BT1-4F10 epitope appeared to be restricted to Microchiropteran immunoglobulins and absent from Megachiropteran immunoglobulins. Analyses of sera and other E. fuscus fluids showed that most, if not all, secreted immunoglobulins utilized lambda light chains. Finally, mAb BT1-4F10 permitted the identification of B cell follicles in splenic white pulp. This Microchiropteran-specific mAb has potential utility in seroassays;hence, this reagent may have both basic and practical applications for studying immune process. (C) 2016 Elsevier Ltd. All rights reserved.

关键词： influenza   orthomyxoviridae   emerging viruses   bat   chiroptera  

摘要： Two novel influenza A-like viral genome sequences have recently been identified in Central and South American fruit bats and provisionally designated "HL17NL10" and "HL18NL11." All efforts to isolate infectious virus from bats or to generate these viruses by reverse genetics have failed to date. Recombinant vesicular stomatitis virus (VSV) encoding the hemagglutinin-like envelope glycoproteins HL17 or HL18 in place of the VSV glycoprotein were generated to identify cell lines that are susceptible to bat influenza A-like virus entry. More than 30 cell lines derived from various species were screened but only a few cell lines were found to be susceptible, including Madin-Darby canine kidney type II (MDCK II) cells. The identification of cell lines susceptible to VSV chimeras allowed us to recover recombinant HL17NL10 and HL18NL11 viruses from synthetic DNA. Both influenza A-like viruses established a productive infection in MDCK II cells;however, HL18NL11 replicated more efficiently than HL17NL10 in this cell line. Unlike conventional influenza A viruses, bat influenza A-like viruses started the infection preferentially at the basolateral membrane of polarized MDCK II cells;however, similar to conventional influenza A viruses, bat influenza A-like viruses were released primarily from the apical site. The ability of HL18NL11 or HL17NL10 viruses to infect canine and human cells might reflect a zoonotic potential of these recently identified bat viruses.

关键词： Filovirus   Ebolavirus   Sub-Saharan Africa   Guinea   Migration   Rainforests   Megachiroptera  

摘要： Both Ebolavirus and Marburgvirus were detected in several fruit bat species of the family Pteropodidae, suggesting that this taxon plays a key role in the life cycle of filoviruses. After four decades of Zaire Ebolavirus (ZEBOV) outbreaks in Central Africa, the virus was detected for the first time in West Africa in 2014. To better understand the role of fruit bats as potential reservoirs and circulating hosts between Central and West Africa, we examine here the phylogeny and comparative phylogeography of Pteropodidae. Our phylogenetic results confirm the existence of four independent lineages of African fruit bats: the genera Eidolon and Rousettus, and the tribes Epomophorini and Scotonycterini, and indicate that the three species suspected to represent ZEBOV reservoir hosts (Epomops franqueti, Hypsignathus monstrosus, and Myonycteris torquata) belong to an African clade that diversified rapidly around 8-7 Mya. To test for phylogeographic structure and for recent gene flow from Central to West Africa, we analysed the nucleotide variation of 675 cytochrome b gene (Cytb) sequences, representing eight fruit bat species collected in 48 geographic localities. Within Epomophorina, our mitochondrial data do not support the monophyly of two genera (Epomops and Epomophorus) and four species (Epomophorus gambianus, Epomops franqueti, Epomops buettikoferi, and Micropteropus pusillus). In Epomops, however, we found two geographic haplogroups corresponding to the Congo Basin and Upper Guinea forests, respectively. By contrast, we found no genetic differentiation between Central and West African populations for all species known to make seasonal movements, Eidolon helvum, E. gambianus, H. monstrosus, M. pusillus, Nanonycteris veldkampii, and Rousettus aegyptiacus. Our results suggest that only three fruit bat species were able to disperse directly ZEBOV from the Congo Basin to Upper Guinea: E. helvum, H. monstrosus, and R. aegyptiacus. (C) 2016 Academie des sciences. Published b