Cedar Virus: A Novel Henipavirus Isolated from Australian Bats

The genus Henipavirus in the family Paramyxoviridae contains two viruses, Hendra virus (HeV) and Nipah virus (NiV) for which pteropid bats act as the main natural reservoir. Each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis. Here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, Cedar virus (CedPV), which shares significant features with the known henipaviruses. The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrin- B2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. In this context, it is interesting to note that the major genetic difference between CedPV and HeV or NiV lies within the coding strategy of the P gene, which is known to play an important role in evading the host innate immune system. Unlike HeV, NiV, and almost all known paramyxoviruses, the CedPV P gene lacks both RNA editing and also the coding capacity for the highly conserved V protein. Preliminary study indicated that CedPV infection of human cells induces a more robust IFN-β response than HeV.     

Henipavirus neutralising antibodies in an isolated island population of African fruit bats

Isolated islands provide valuable opportunities to study the persistence of viruses in wildlife populations, including population size thresholds such as the critical community size. The straw-coloured fruit bat, Eidolon helvum, has been identified as a reservoir for henipaviruses (serological evidence) and Lagos bat virus (LBV; virus isolation and serological evidence) in continental Africa. Here, we sampled from a remote population of E. helvum annobonensis fruit bats on Annobón island in the Gulf of Guinea to investigate whether antibodies to these viruses also exist in this isolated subspecies. Henipavirus serological analyses (Luminex multiplexed binding and inhibition assays, virus neutralisation tests and western blots) and lyssavirus serological analyses (LBV: modified Fluorescent Antibody Virus Neutralisation test, LBV and Mokola virus: lentivirus pseudovirus neutralisation assay) were undertaken on 73 and 70 samples respectively. Given the isolation of fruit bats on Annobón and their lack of connectivity with other populations, it was expected that the population size on the island would be too small to allow persistence of viruses that are thought to cause acute and immunising infections. However, the presence of antibodies against henipaviruses was detected using the Luminex binding assay and confirmed using alternative assays. Neutralising antibodies to LBV were detected in one bat using both assays. We demonstrate clear evidence for exposure of multiple individuals to henipaviruses in this remote population of E. helvum annobonensis fruit bats on Annobón island. The situation is less clear for LBV. Seroprevalences to henipaviruses and LBV in Annobón are notably different to those in E. helvum in continental locations studied using the same sampling techniques and assays. Whilst cross-sectional serological studies in wildlife populations cannot provide details on viral dynamics within populations, valuable information on the presence or absence of viruses may be obtained and utilised for informing future studies.     

Functional Rectification of the Newly Described African Henipavirus Fusion Glycoprotein (Gh-M74a)

Recent evidence identified multiple Henipavirus species in Africa distinct from those in Southeast Asia and Australia. The reported fusion glycoprotein (F) sequence of the African Gh-M74a strain (GhV-F) is likely incorrect: a single base pair deletion near the N terminus results in multiple aberrancies. Rectifying this by adding single nucleotide insertions results in a GhV-F that now possesses a signal peptide, is efficiently cell surface expressed, exhibits syncytium formation when coexpressed with GhV-G protein, and mediates pseudotyped viral particle entry.     

Surface Glycoproteins of an African Henipavirus Induce Syncytium Formation in a Cell Line Derived from an African Fruit Bat,Hypsignathus monstrosus

Serological screening and detection of genomic RNA indicates that members of the genus Henipavirus are present not only in Southeast Asia but also in African fruit bats. We demonstrate that the surface glycoproteins F and G of an African henipavirus (M74) induce syncytium formation in a kidney cell line derived from an African fruit bat, Hypsignathus monstrosus. Despite a less broad cell tropism, the M74 glycoproteins show functional similarities to glycoproteins of Nipah virus.     

Henipavirus Pathogenesis in Human Respiratory Epithelial Cells

Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection.     

新疆部分地区动物Nipah病毒和Hendra病毒感染的调查

拟建立一步法实时RT-PCR检测Nipah病毒(Nipah virus,NiV)、Hendra病毒(Hendra virus,HeV)的方法,对采集自中国新疆部分地区动物外周血样本进行NiV和HeV检测,以获得我国新疆地区的NiV和HeV的病毒流行病学资料.采用NiV和HeV一步法实时RT-PCR检测方法,对2007年9-12月采集的新疆伊犁河谷地区以及巴音布鲁克草原放养的500匹马、100匹驴和160只犬外周血单个核细胞RNA进行NiV和HeV N基因片段检测.结果:对采集的动物血样本进行NiV和HeV核酸检测,成功进行了一步法实时RT-PCR反应,没有发现阳性样本.初步流行病学研究提示我国新疆部分地区天然牧场放养的动物中可能不存在NiV和HeV感染,该地区出现NiV和HeV爆发的可能性较小.     

Modes of paramyxovirus fusion: a Henipavirus perspective

Henipavirus is a new genus of Paramyxoviridae that uses protein-based receptors (ephrinB2 and ephrinB3) for virus entry. Paramyxovirus entry requires the coordinated action of the fusion (F) and attachment viral envelope glycoproteins. Receptor binding to the attachment protein triggers F to undergo a conformational cascade that results in membrane fusion. The accumulation of structural and functional studies on many paramyxoviral fusion and attachment proteins, including the recent elucidation of structures of Nipah virus (NiV) and Hendra virus (HeV) G glycoproteins bound and unbound to cognate ephrinB receptors, indicate that henipavirus entry and fusion could differ mechanistically from paramyxoviruses that use glycan-based receptors.     

Optimizing Viral Discovery in Bats

Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007–2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches.     

Personality Variation in Little Brown Bats

Animal personality or temperament refers to individual differences in behaviour that are repeatable over time and across contexts. Personality has been linked to life-history traits, energetic traits and fitness, with implications for the evolution of behaviour. Personality has been quantified for a range of taxa (e.g., fish, songbirds, small mammals) but, so far, there has been little work on personality in bats, despite their diversity and potential as a model taxon for comparative studies. We used a novel environment test to quantify personality in little brown bats (Myotis lucifugus) and assess the short-term repeatability of a range of behaviours. We tested the hypothesis that development influences values of personality traits and predicted that trait values associated with activity would increase between newly volant, pre-weaning young-of-the-year (YOY) and more mature, self-sufficient YOY. We identified personality dimensions that were consistent with past studies of other taxa and found that these traits were repeatable over a 24-hour period. Consistent with our prediction, older YOY captured at a fall swarming site prior to hibernation had higher activity scores than younger YOY bats captured at a maternity colony, suggesting that personality traits vary as development progresses in YOY bats. Thus, we found evidence of short-term consistency of personality within individuals but with the potential for temporal flexibility of traits, depending on age.     

回声定位蝙蝠及其声通讯

综述了回声定位蝙蝠种类及其发声方式,回声定位信号的主要类型及回声定位信号声学特征,多普勒频移对长CF／FM蝙蝠的主要作用,简介了蝙蝠求偶和母婴识别等内声通讯行为,提出了一些尚待解决的重要问题。     

Bats Fertilize Roost Trees

Using nitrogen isotope ratio as proxy for nutrient transfer, we tracked nutrients from bat excreta to seed exocarp in Dipteryx panamensis that host bat roosts, suggesting that trees may benefit from nutrients of bat guano deposited into hollow tree trunks.     

Dampened STING-Dependent Interferon Activation in Bats

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大围山里寻蝙蝠

壬午年末,北国正是银装素裹、呵气成霜的时节,我们为了进行蝙蝠系统发育研究,来到了素有“彩云之南”、“野生动植物王国“美称的云南省东南部,探访生活在祖国边陲的小鬼头。 云南省是我国蝙蝠最丰富的地区,位于屏边县的大围山是我们选择的重要目的地之一。早在上个世纪50年代,中国科学院动物所的老前辈们曾经来到这里采集了大量蝙蝠标本,正所谓“前人栽树,后人乘凉”,我们得益于这些丰富的历史资料所提供的重要信息,也使我们下定决心要来此看一看。 屏边县城是一个很小的地方,但却流露出与大城市不同的、几分难得的幽静和安逸。大围山自然保护区管理所副所长何永明先生及其同事热情欢迎我们这些慕名远道而来的探访者。     

Mitochondrial RNA and protein synthesis in enucleated African green monkey cells

The behavior of extramitochondrial protein synthesis and of mitochondrial RNA and protein synthesis was examined in the cytoplasts of African green monkey kidney cells (TC-7 subline) at different times following enucleation by cytochalasin B. The rate of incorporation of [³H]isoleucine into protein of the soluble cytoplasmic fraction decreased in an approximately exponential fashion, with a half-life of about five hours, during the first 26 hours after enucleation. Discrete mitochondrial 16 S, 12 S and 4 S RNA components were identified among the products of cytoplast RNA synthesis. The rates of [³H]uridine incorporation into the 16 and 12 S RNA components as well as into total RNA declined progressively after enucleation to a barely detectable level by the 20th hour. By contrast, the rate of chloramphenicol-sensitive [³H]isoleucine incorporation into protein (due to mitochondrial protein synthesis) did not undergo a substantial decline for at least 20 hours in TC-7 cytoplasts; instead, a reproducible transient stimulation occurred in the first hours following enucleation. The products of mitochondrial protein synthesis pulse-labeled in nucleated cells and in cytoplasts 24 hours after enucleation exhibited similar electrophoretic profiles.     

Serological Evidence of Henipavirus Exposure in Cattle,Goats and Pigs in Bangladesh

Background

Nipah virus (NiV) is an emerging disease that causes severe encephalitis and respiratory illness in humans. Pigs were identified as an intermediate host for NiV transmission in Malaysia. In Bangladesh, NiV has caused recognized human outbreaks since 2001 and three outbreak investigations identified an epidemiological association between close contact with sick or dead animals and human illness.

Methodology

We examined cattle and goats reared around Pteropus bat roosts in human NiV outbreak areas. We also tested pig sera collected under another study focused on Japanese encephalitis.

Principal Findings

We detected antibodies against NiV glycoprotein in 26 (6.5%) cattle, 17 (4.3%) goats and 138 (44.2%) pigs by a Luminex-based multiplexed microsphere assay; however, these antibodies did not neutralize NiV. Cattle and goats with NiVsG antibodies were more likely to have a history of feeding on fruits partially eaten by bats or birds (PR = 3.1, 95% CI 1.6–5.7) and drinking palmyra palm juice (PR = 3.9, 95% CI 1.5–10.2).

Conclusions

This difference in test results may be due to the exposure of animals to one or more novel viruses with antigenic similarity to NiV. Further research may identify a novel organism of public health importance.