关键词： Ebola virus   filovirus   emerging viruses   bats   reservoir biology   viral evolution   evolution   ADAR   population genetics  

摘要： Ebola virus (EBOV) causes a severe, often fatal disease in humans and nonhuman primates. Within the past decade, EBOV has caused two large and difficult-to-control outbreaks, one of which recently ended in the Democratic Republic of the Congo. Bats are the likely reservoir of EBOV, but little is known of their relationship with the virus. We perform serial passages of EBOV in human and bat cells and use circular sequencing to compare the short-term evolution of the virus. Virus populations passaged in bat cells have sequence markers indicative of host RNA editing enzyme activity, including evidence for ADAR editing of the EBOV glycoprotein. Multiple regions in the EBOV genome appear to have undergone adaptive evolution when passaged in bat and human cells. Individual mutated viruses are rescued and characterized. Our results provide insight into the host species-specific evolution of EBOV and highlight the adaptive flexibility of the virus.

关键词： 蝙蝠蛾被毛孢菌丝体   小鼠   免疫功能   腺苷   HPLC  

摘要： 目的:探讨蝙蝠蛾被毛孢菌丝体对小鼠的免疫调节作用,并分析其可能的功效成分。方法:采用高效液相色谱法测定菌丝体中的腺苷含量;分别经口连续给予小鼠0.08、0.17、0.50 g/kg bw·d剂量的30 d后,进行各项免疫指标的测定。结果:蝙蝠蛾被毛孢菌丝体中腺苷含量达275 mg/100 g;在免疫调节方面,0.50 g/kg bw·d剂量组加ConA孔与不加ConA孔吸光度的差值、耳壳增重、小鼠溶血空斑数、NK细胞活性均高于对照组,差异有统计学意义(P<0.05);0.17 g/kg bw·d和0.50 g/kg bw·d组小鼠血清半数溶血值(HC50)显著高于对照组(P<0.05)。结论:蝙蝠蛾被毛孢菌丝体具有调节小鼠免疫功能作用,此作用与其主要功效成分腺苷有关。

关键词： Adeno-associated virus   Pre-existing antibodies   cryo-EM   Virus capsid  

摘要： Adeno-associated viruses (AAVs) are widespread among vertebrates. AAVs isolated from bats display low capsid protein sequence identities (< 60%) to AAV2, AAV5, and other primate AAVs. Here we report the first capsid structure of a non-primate AAV which was isolated from bats. The capsid structure of BtAAV-10HB (10HB) was determined by cryo-electron microscopy and three-dimensional image reconstruction to 3.03 angstrom resolution. Comparison of empty and genome-containing capsids showed that the capsid structures are almost identical except for an ordered nucleotide in a previously described nucleotide-binding pocket, the density in the 5-fold channel, and several amino acids with altered side chain conformations. Compared to other dependoparvo-viruses, for example AAV2 and AAV5, 10HB displays unique structural features including insertions and deletions in capsid surface loops. Overall, the 10HB capsid structure superposes with an RMSD of 1.7 angstrom and 1.8 angstrom to AAV2 and AAV5, respectively. Currently all approved AAV human gene therapy biologics and vectors in clinical trials are based on primate isolates. However, pre-existing neutralizing antibodies in the human population represents a hurdle to their use. 10HB capsids are capable of packaging AAV2 vector genomes and thus have potential as gene delivery vectors. Significantly, a screen with human sera showed lack of recognition by the 10HB capsid. Thus, the different capsid surface of 10HB vectors likely renders it "invisible" to potential preexisting neutralizing human anti-AAV antibodies especially because this virus or similar variants do not exist in primate populations.

关键词： Cryoelectron microscopy   SARS-CoV-2  

摘要： SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S;we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor. Cryo-EM and functional analyses of furin-cleaved spike from SARS-CoV-2 and the closely related spike from bat virus RaTG13 reveal differences in protein stability and binding to human receptor ACE2.

摘要： ObjectiveTo better understand the potential risks of Nipah virus emergence in Cambodia by studying different components of the interface between humans and bats. Methods From 2012 to 2016, we conducted a study at two sites in Kandal and Battambang provinces where fruit bats (Pteropus lylei) roost. We combined research on: bat ecology (reproductive phenology, population dynamics and diet);human practices and perceptions (ethnographic research and a knowledge, attitude and practice study);and Nipah virus circulation in bat and human populations (virus monitoring in bat urine and anti-Nipah-virus antibody detection in human serum). Findings Our results confirmed circulation of Nipah virus in fruit bats (28 of 3930 urine samples positive by polymerase chain reaction testing). We identified clear potential routes for virus transmission to humans through local practices, including fruit consumed by bats and harvested by humans when Nipah virus is circulating, and palm juice production. Nevertheless, in the serological survey of 418 potentially exposed people, none of them were seropositive to Nipah virus. Differences in agricultural practices among the regions where Nipah virus has emerged may explain the situation in Cambodia and point to actions to limit the risks of virus transmission to humans. Conclusion Human practices are key to understanding transmission risks associated with emerging infectious diseases. Social science disciplines such as anthropology need to be integrated in health programmes targeting emerging infectious diseases. As bats are hosts of major zoonotic pathogens, such integrated studies would likely also help to reduce the risk of emergence of other bat-borne diseases.

关键词： Ebola virus   SARS-CoV-2   Viral infection   Viral reservoirs  

摘要： Most viral pathogens in humans have animal origins and arose through cross-species transmission. Over the past 50 years, several viruses, including Ebola virus, Marburg virus, Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory coronavirus (MERS-CoV) and SARS-CoV-2, have been linked back to various bat species. Despite decades of research into bats and the pathogens they carry, the fields of bat virus ecology and molecular biology are still nascent, with many questions largely unexplored, thus hindering our ability to anticipate and prepare for the next viral outbreak. In this Review, we discuss the latest advancements and understanding of bat-borne viruses, reflecting on current knowledge gaps and outlining the potential routes for future research as well as for outbreak response and prevention efforts. Bats harbour a large number of different viruses, some of which have spilled over to cause human disease. In this Review, Letko, Munster and colleagues discuss the diversity of bat viruses and the factors that determine the emergence of zoonotic viruses from bats.

关键词： Bats   Aging   Longevity   Inflammation   Inflammaging  

摘要： For centuries, people believed that bats possessed sinister powers. Bats are thought to be ancestral hosts to many deadly viruses affecting humans including Ebola, rabies, and most recently SARS-CoV-2 coronavirus. However, bats themselves tolerate these viruses without ill effects. The second power that bats have is their longevity. Bats live much longer than similar-sized land mammals. Here we review how bats' ability to control inflammation may be contributing to their longevity. The underlying mechanisms may hold clues to developing new treatments for age-related diseases. Now may be the time to use science to exploit the secret powers of bats for human benefit.

关键词： Bat   EMCV   JEV   PRRs   IFN-beta  

摘要： Bats are potential natural hosts of Encephalomyocarditis virus (EMCV) and Japanese encephalitis virus (JEV). Bats appear to have some unique features in their innate immune system that inhibit viral replication causing limited clinical symptoms, and thus, contributing to the virus spill over to humans. Here, kidney epithelial cell lines derived from four bat species (Pteropus dasymallus, Rousettus leschenaultii, Rhinolophus ferrumequinum, and Miniopterus fuliginosus) and two non-bat species (Homo sapiens and Mesocricetus auratus) were infected with EMCV and JEV. The replication of EMCV and JEV was lower in the bat cell lines derived from R. leschenaultii, R. ferrumequinum, and M. fuliginosus with a higher expression level of pattern recognition receptors (PRRs) (TLR3, RIG-I, and MDA5) and interferon-beta (IFN-beta) than that in the non-bat cell lines and a bat cell line derived from P. dasymallus. The knockdown of TLR3, RIG-I, and MDA5 in Rhinolophus bat cell line using antisense RNA oligonucleotide led to decrease IFN-b expression and increased viral replication. These results suggest that TLR3, RIG-I, and MDA5 are important for antiviral response against EMCV and JEV in Rhinolophus bats. (c) 2020 Elsevier Inc. All rights reserved.