- Volume 104, Issue 4, 2023
Volume 104, Issue 4, 2023
- Reviews
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A review of reptile virus experimental infection studies
More LessDespite recent advances in molecular techniques, infection studies remain an important tool for biosecurity, veterinary and conservation medicines. Experimental infection studies are performed for many reasons: to investigate causal links between pathogens and disease, to study host species susceptibility, to study immune response to inoculation, to investigate pathogen transmission and to investigate methods for infection control. Experimental infection studies using viruses in reptiles have been conducted sporadically since at least the 1930s and this continues to be a fertile area of research. This review catalogues previously published research in the field. The key parameters of each study are tabulated, providing a summary of more than 100 experiments linked to their original publications. Common themes and trends within the data are discussed.
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The role of sand flies as vectors of viruses other than phleboviruses
More LessSand flies (Diptera: Phlebotominae) are proven vectors of various pathogens of medical and veterinary importance. Although mostly known for their pivotal role in the transmission of parasitic protists of the genus Leishmania that cause leishmaniases, they are also proven or suspected vectors of many arboviruses, some of which threaten human and animal health, causing disorders such as human encephalitis (Chandipura virus) or serious diseases of domestic animals (vesicular stomatitis viruses). We reviewed the literature to summarize the current published information on viruses detected in or isolated from phlebotomine sand flies, excluding the family Phenuiviridae with the genus Phlebovirus, as these have been well investigated and up-to-date reviews are available. Sand fly-borne viruses from four other families (Rhabdoviridae, Flaviviridae, Reoviridae and Peribunyaviridae) and one unclassified group (Negevirus) are reviewed for the first time regarding their distribution in nature, host and vector specificity, and potential natural transmission cycles.
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Mechanisms of bunyavirus morphogenesis and egress
More LessUnlike many segmented negative-sense RNA viruses, most members of the Bunyavirales bud at Golgi membranes, as opposed to the plasma membrane. Central players in this assembly process are the envelope glycoproteins, Gn and Gc, which upon translation undergo proteolytic processing, glycosylation and trafficking to the Golgi, where they interact with ribonucleoprotein genome segments and bud into Golgi-derived compartments. The processes involved in genome packaging during virion assembly can lead to the generation of reassorted viruses, if a cell is co-infected with two different bunyaviruses, due to mismatching of viral genome segment packaging. This can lead to viruses with high pathogenic potential, as demonstrated by the emergence of Schmallenberg virus. This review focuses on the assembly pathways of tri-segmented bunyaviruses, highlighting some areas in need of further research to understand these important pathogens with zoonotic potential.
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- ICTV Virus Taxonomy Profiles
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ICTV Virus Taxonomy Profile: Simuloviridae 2023
The family Simuloviridae includes tailless icosahedral viruses with an internal lipid membrane. The capsid is constructed from two major capsid proteins, both with a single jelly-roll fold. The genome is a circular dsDNA molecule of 16–19 kb. All members infect halophilic archaea in the class Halobacteria (phylum Euryarchaeota) and are temperate viruses, their proviruses residing in host cells as extrachromosomal episomes. Once the lytic life cycle is triggered, production of virions causes cell lysis. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Simuloviridae, which is available at ictv.global/report/simuloviridae.
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ICTV Virus Taxonomy Profile: Coronaviridae 2023
The family Coronaviridae includes viruses with positive-sense RNA genomes of 22–36 kb that are expressed through a nested set of 3′ co-terminal subgenomic mRNAs. Members of the subfamily Orthocoronavirinae are characterized by 80–160 nm diameter, enveloped virions with spike projections. The orthocoronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome-related coronavirus are extremely pathogenic for humans and in the last two decades have been responsible for the SARS and MERS epidemics. Another orthocoronavirus, severe acute respiratory syndrome coronavirus 2, was responsible for the recent global COVID-19 pandemic. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Coronaviridae which is available at www.ictv.global/report/coronaviridae.
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- Animal
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- RNA Viruses
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Mass mortality among colony-breeding seabirds in the German Wadden Sea in 2022 due to distinct genotypes of HPAIV H5N1 clade 2.3.4.4b
Mass mortality was observed among colony-breeding seabirds in the German Wadden Sea area of the North Sea during the summer months of 2022. Several species’ colonies were affected, most notably sandwich terns (Thalasseus sandvicensis), common terns (Sterna hirundo) and Germany’s only northern gannet (Morus bassanus) colony on the island of Heligoland. Mortality in some tern colonies reached 40%, while other colonies were almost spared. In all cases, infections with the high-pathogenicity avian influenza virus (HPAIV) subtype H5N1 of clade 2.3.4.4b were identified to have caused the epidemic. Phylogenetic analysis of whole-genome sequences revealed that the outbreaks were dominated by two genotypes, Ger-10–21 N1.2 and Ger-10–21 N1.5, previously identified in Germany. Spatiotemporal analyses of phylogenetic data suggested that these viruses could have entered the continental North Sea coastal region via the British Isles. A close linkage of viruses from tern colonies in the German Wadden Sea was evident with further connections to breeding colonies in Belgium and the Netherlands, and further spread to Denmark and Poland. Several of the affected species are endangered, such that negative effects of epizootic HPAIV infections on populations are feared, with uncertain long-term consequences.
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An oseltamivir-resistant avian H1N1 influenza A virus can transmit from mallards to chickens similarly to a wild-type strain: implications for the risk of resistance transmission to humans
The neuraminidase inhibitor (NAI) oseltamivir is stockpiled globally as part of influenza pandemic preparedness. However, oseltamivir carboxylate (OC) resistance develops in avian influenza virus (AIV) infecting mallards exposed to environmental-like OC concentrations, suggesting that environmental resistance is a real concern. Herein we used an in vivo model to investigate if avian influenza H1N1 with the OC-resistant mutation NA-H274Y (51833/H274Y) as compared to the wild-type (wt) strain (51833 /wt) could transmit from mallards, which would potentially be exposed to environmentally contaminated environments, to and between chickens, thus posing a potential zoonotic risk of antiviral-resistant AIV. Regardless of whether the virus had the OC-resistant mutation or not, chickens became infected both through experimental infection, and following exposure to infected mallards. We found similar infection patterns between 51833/wt and 51833/H274Y such that, one chicken inoculated with 51833/wt and three chickens inoculated with 51833/H274Y were AIV positive in oropharyngeal samples more than 2 days consecutively, indicating true infection, and one contact chicken exposed to infected mallards was AIV positive in faecal samples for 3 consecutive days (51833/wt) and another contact chicken for 4 consecutive days (51833/H274Y). Importantly, all positive samples from chickens infected with 51833/H274Y retained the NA-H274Y mutation. However, none of the virus strains established sustained transmission in chickens, likely due to insufficient adaptation to the chicken host. Our results demonstrate that an OC-resistant avian influenza virus can transmit from mallards and replicate in chickens. NA-H274Y does not constitute a barrier to interspecies transmission per se, as the resistant virus did not show reduced replicative capacity compared to the wild-type counterpart. Thus, responsible use of oseltamivir and surveillance for resistance development is warranted to limit the risk of an OC-resistant pandemic strain.
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Digoxin is a potent inhibitor of Bunyamwera virus infection in cell culture
More LessDrug repurposing is a valuable source of new antivirals because many compounds used to treat a variety of pathologies can also inhibit viral infections. In this work, we have tested the antiviral capacity of four repurposed drugs to treat Bunyamwera virus (BUNV) infection in cell cultures. BUNV is the prototype of the Bunyavirales order, a large group of RNA viruses that includes important pathogens for humans, animals and plants. Mock- and BUNV-infected Vero and HEK293T cells were treated with non-toxic concentrations of digoxin, cyclosporin A, sunitinib and chloroquine. The four drugs inhibited BUNV infection with varying potency in Vero cells, and all except sunitinib also in HEK293T cells, with digoxin rendering the lowest half maximal inhibitory concentration (IC50). Since digoxin rendered the best results, we selected this drug for a more detailed study. Digoxin is an inhibitor of the Na+/K+ ATPase, a plasma membrane enzyme responsible for the energy-dependent exchange of cytoplasmic Na+ for extracellular K+ in mammalian cells and involved in many signalling pathways. Digoxin was shown to act at an early time point after viral entry reducing the expression of the viral proteins Gc and N. Effects on the cell cycle caused by BUNV and digoxin were also analysed. In Vero cells, digoxin favoured the transition from G1 phase of the cell cycle to S phase, an effect that might contribute to the anti-BUNV effect of digoxin in this cell type. Transmission electron microscopy showed that digoxin impedes the assembly of the characteristic spherules that harbour the BUNV replication complexes and the morphogenesis of new viral particles. Both BUNV and digoxin induce similar changes in the morphology of mitochondria that become more electron-dense and have swollen cristae. The alterations of this essential organelle might be one of the factors responsible for digoxin-induced inhibition of viral infection. Digoxin did not inhibit BUNV infection in BHK-21 cells that have a digoxin-resistant Na+/K+ ATPase, which suggests that the effects of the blockade of this enzyme is a key factor of the antiviral activity of digoxin in BUNV-infected Vero cells.
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Replication and innate immune responses of two chikungunya virus genotypes in human monocyte-derived macrophages
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which causes epidemics of fever, joint pain and rash. There are three genotypes: West African, East/Central/South/Africa (ECSA) and Asian, with the latter two predominant globally. Genotype-specific differences in clinical presentations, virulence and immunopathology have been described. Macrophages are key cells in immune responses against CHIKV. Circulating blood monocytes enter tissue to differentiate into monocyte-derived macrophages (MDMs) in response to CHIKV infection at key replication sites such as lymphoid organs and joints. This study analyses differences in replication and induced immune mediators following infection of MDMs with Asian and ECSA CHIKV genotypes. Primary human MDMs were derived from residual blood donations. Replication of Asian (MY/06/37348) or ECSA (MY/08/065) genotype strains of CHIKV in MDMs was measured by plaque assay. Nineteen immune mediators were measured in infected cell supernatants using multiplexed immunoassay or ELISA. MY/08/065 showed significantly higher viral replication at 24 h post-infection (h p.i.) but induced significantly lower expression of proinflammatory cytokines (CCL-2, CCL-3, CCL-4, RANTES and CXCL-10) and the anti-inflammatory IL-1Ra compared to MY/06/37348. No differences were seen at later time points up to 72 h p.i. During early infection, MY/08/065 induced lower proinflammatory immune responses in MDMs. In vivo, this may lead to poorer initial control of viral infection, facilitating CHIKV replication and dissemination to other sites such as joints. This may explain the consistent past findings that the ECSA genotype is associated with greater viremia and severity of symptoms than the Asian genotype. Knowledge of CHIKV genotype-specific immunopathogenic mechanisms in human MDMs is important in understanding of clinical epidemiology, biomarkers and therapeutics in areas with co-circulation of different genotypes.
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Swine IFI6 confers antiviral effects against Japanese encephalitis virus in vitro and in vivo
More LessSwine are considered to be an important intermediate host in the cycle of Japanese encephalitis virus (JEV) infection. Most existing antiviral studies of JEV mainly focus on the host factor of the dead-end hosts. However, little research has addressed this in swine. Here, we found that swine interferon alpha-inducible protein 6 (sIFI6) possessed antiviral activity against JEV. In vitro studies showed that overexpression of sIFI6 inhibited the infection of JEV, while sIFI6 knockdown enhanced the infection of JEV in PK-15 cells. In addition, we also found that the structural integrity of sIFI6 was required by anti-JEV activity and that sIFI6 interacted with JEV nonstructural protein 4A (NS4A), an integral membrane protein with a pivotal function in replication complex during JEV replication. The interaction domain was mapped to the fourth transmembrane domain (TMD), also known as the 2K peptide of NS4A. The antiviral activity of sIFI6 was regulated by endoplasmic reticulum (ER) stress-related protein, Bip. In vivo studies revealed that sIFI6 alleviated symptoms of JEV infection in C57BL/6 mice. In addition, the antiviral spectrum of sIFI6 showed that sIFI6 specifically inhibited JEV infection. In conclusion, this study identified sIFI6 as a host factor against JEV infection for the first time. Our findings provide a potential drug target against JEV infection.
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- DNA Viruses
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Codon pair bias deoptimization of essential genes in infectious laryngotracheitis virus reduces protein expression
More LessInfectious laryngotracheitis virus (ILTV; an alphaherpesvirus) is a respiratory pathogen of chickens and causes significant economic losses in the poultry industry globally, in addition to severe animal health and welfare concerns. To date, studying the role of ILTV genes in viral infection, replication or pathogenesis has largely been limited to genes that can be deleted from the ILTV genome and the resultant deletion mutants characterized in vitro or in vivo. However, this approach is not suitable for the study of essential genes. This study trialled two different codon deoptimization techniques that aimed to separately disrupt and downregulate the expression of two ILTV genes, ICP8 and UL12, which are essential or very important in viral replication. The target genes were partially recoded using codon usage deoptimization (CUD) and codon pair bias deoptimization (CPBD) approaches and characterized in vitro. Viruses deoptimized via CPBD showed decreased protein expression as assessed by Western blotting and/or fluorescence microscopy to measure the intensity of the fluorescent marker fused to the target protein. Viruses deoptimized by CUD showed less consistent results, with some mutants that could not be generated or isolated. The results indicate that CPBD is an attractive and viable tool for the study of essential or critically important genes in ILTV. This is the first study, to our knowledge, that utilizes CPBD and CUD techniques for the study of ILTV genes.
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Time series prediction for the epidemic trends of monkeypox using the ARIMA, exponential smoothing, GM (1, 1) and LSTM deep learning methods
Monkeypox is a critical public health emergency with international implications. Few confirmed monkeypox cases had previously been reported outside endemic countries. However, since May 2022, the number of monkeypox infections has increased exponentially in non-endemic countries, especially in North America and Europe. The objective of this study was to develop optimal models for predicting daily cumulative confirmed monkeypox cases to help improve public health strategies. Autoregressive integrated moving average (ARIMA), exponential smoothing, long short-term memory (LSTM) and GM (1, 1) models were employed to fit the cumulative cases in the world, the USA, Spain, Germany, the UK and France. Performance was evaluated by minimum mean absolute percentage error (MAPE), among other metrics. The ARIMA (2, 2, 1) model performed best on the global monkeypox dataset, with a MAPE value of 0.040, while ARIMA (2, 2, 3) performed the best on the USA and French datasets, with MAPE values of 0.164 and 0.043, respectively. The exponential smoothing model showed superior performance on the Spanish, German and UK datasets, with MAPE values of 0.043, 0.015 and 0.021, respectively. In conclusion, an appropriate model should be selected according to the local epidemic characteristics, which is crucial for monitoring the monkeypox epidemic. Monkeypox epidemics remain severe, especially in North America and Europe, e.g. in the USA and Spain. The development of a comprehensive, evidence-based scientific programme at all levels is critical to controlling the spread of monkeypox infection.
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- Plant
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- RNA viruses
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Engineering aphid transmission of foxtail mosaic virus in the presence of potyvirus helper component proteinase through coat protein modifications
More LessBiotechnologies that use plant viruses as plant enhancement tools have shown great potential to flexibly engineer crop traits, but field applications of these technologies are still limited by efficient dissemination methods. Potyviruses can be rapidly inoculated into plants by aphid vectors due to the presence of the potyviral helper component proteinase (HC-Pro), which binds to the DAG motif of the coat protein (CP) of the virion. Previously it was determined that a naturally occurring DAG motif in the non-aphid-transmissible potexvirus, potato aucuba mosaic virus (PAMV), is functional when a potyviral HC-Pro is provided to aphids in plants. The DAG motif of PAMV was successfully transferred to the CP of another non-aphid-transmissible potexvirus, potato virus X, to convey aphid transmission capabilities in the presence of HC-Pro. Here, we demonstrate that DAG-containing segments of the CP from two different potyviruses (sugarcane mosaic virus and turnip mosaic virus), and from the previously used potexvirus, PAMV, can make the potexvirus, foxtail mosaic virus (FoMV), aphid-transmissible when fused with the FoMV CP. We show that DAG-containing FoMVs are transmissible by aphids that have prior access to HC-Pro through potyvirus-infected plants or ectopic expression of HC-Pro. The transmission efficiency of the DAG-containing FoMVs varied from less than 10 % to over 70 % depending on the length and composition of the surrounding amino acid sequences of the DAG-containing segment, as well as due to the recipient plant species. Finally, we show that the engineered aphid-transmissible FoMV is still functional as a plant enhancement resource, as endogenous host target genes were silenced in FoMV-infected plants after aphid transmission. These results suggest that aphid transmission could be engineered into non-aphid-transmissible plant enhancement viral resources to facilitate their field applications.
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Volumes and issues
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Volume 105 (2024)
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Volume 104 (2023)
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Volume 103 (2022)
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Volume 102 (2021)
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Volume 101 (2020)
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Volume 100 (2019)
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Volume 99 (2018)
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Volume 98 (2017)
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Volume 97 (2016)
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Volume 96 (2015)
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Volume 95 (2014)
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Volume 94 (2013)
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Volume 93 (2012)
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Volume 92 (2011)
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Volume 91 (2010)
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Volume 90 (2009)
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Volume 89 (2008)
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Volume 88 (2007)
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Volume 87 (2006)
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Volume 86 (2005)
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Volume 85 (2004)
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Volume 84 (2003)
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Volume 83 (2002)
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Volume 82 (2001)
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Volume 81 (2000)
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Volume 80 (1999)
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Volume 79 (1998)
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Volume 78 (1997)
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Volume 77 (1996)
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Volume 76 (1995)
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Volume 75 (1994)
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Volume 74 (1993)
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Volume 73 (1992)
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Volume 72 (1991)
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Volume 71 (1990)
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Volume 70 (1989)
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Volume 69 (1988)
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Volume 68 (1987)
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Volume 67 (1986)
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Volume 66 (1985)
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Volume 65 (1984)
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Volume 64 (1983)
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Volume 63 (1982)
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Volume 62 (1982)
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Volume 61 (1982)
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Volume 60 (1982)
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Volume 59 (1982)
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Volume 58 (1982)
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Volume 57 (1981)
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Volume 56 (1981)
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Volume 55 (1981)
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Volume 54 (1981)
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Volume 53 (1981)
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Volume 52 (1981)
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Volume 51 (1980)
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Volume 50 (1980)
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Volume 49 (1980)
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Volume 48 (1980)
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Volume 47 (1980)
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Volume 46 (1980)
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Volume 45 (1979)
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Volume 44 (1979)
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Volume 43 (1979)
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Volume 42 (1979)
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Volume 41 (1978)
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Volume 40 (1978)
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Volume 39 (1978)
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Volume 38 (1978)
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Volume 37 (1977)
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Volume 36 (1977)
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Volume 35 (1977)
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Volume 34 (1977)
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Volume 33 (1976)
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Volume 32 (1976)
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Volume 31 (1976)
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Volume 30 (1976)
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Volume 29 (1975)
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Volume 28 (1975)
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Volume 27 (1975)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1974)
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Volume 23 (1974)
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Volume 22 (1974)
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Volume 21 (1973)
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Volume 20 (1973)
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Volume 19 (1973)
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Volume 18 (1973)
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Volume 17 (1972)
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Volume 16 (1972)
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Volume 15 (1972)
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Volume 14 (1972)
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Volume 13 (1971)
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Volume 12 (1971)
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Volume 11 (1971)
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Volume 10 (1971)
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Volume 9 (1970)
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Volume 8 (1970)
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Volume 7 (1970)
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Volume 6 (1970)
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Volume 5 (1969)
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Volume 4 (1969)
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Volume 3 (1968)
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Volume 2 (1968)
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Volume 1 (1967)