Advances in Virus Research最新文献

In the present study, effective inactivation protocols were successfully developed and validated for the two airborne room disinfection methods vaporized hydrogen peroxide (VHP, H₂O₂) and dry fogging of aerosolized peroxyacetic acid (aPAA). Both methods were tested within the same HEPA filter housing (HEPA FH), allowing a direct comparison in an identical experimental setup. This approach provided a detailed comparison of their respective advantages and disadvantages. The main focus was on the determination of the microbicidal efficacy. This is the first time, that the efficacy of both methods has been clearly demonstrated for the most relevant classes of microorganisms using a broad spectrum of different test organisms. During the development phase of the respective optimal inactivation protocols the efficacy of the aPAA process was shown to correspond to the generally accepted microbicidal efficacy profile, whereas the efficacy pattern of the VHP process differed significantly from this. The VHP method demonstrated an exceptionally high sporicidal efficacy, significantly exceeding the measurable antiviral efficacy against both non-enveloped and even enveloped viruses. Moreover, even by reducing the used hydrogen peroxide (HP) amount drastically, no protocol could be applied in which the mycobacterial and the bacterial spore carriers were not be sufficiently inactivated. Based on these clear results, the current practice of using almost exclusively bacterial spore carriers for the establishment and validation of VHP-based inactivation protocols in particular have to be adjusted. Safe and effective inactivation protocols can only be developed by using suitable test organisms adapted to the respective individual requirements.

Concern over spillover events caused by high-consequence pathogens has grown in recent years due to the increased occurrence of such events, and because the COVID-19 pandemic demonstrated how severe the consequences of spillover events can be. As such, there is escalading interest in uncovering the factors that make spillover events more likely, specifically for high-consequence pathogens. An important aspect of this work involves researching how high-consequence pathogens interact with their reservoir hosts. Thus, this chapter discusses the importance of studying high-consequence pathogens in their reservoir hosts, specifically in experimental laboratory settings, with a special emphasis on Sin Nombre virus and Lassa virus, and their respective rodent reservoir hosts, Peromyscus maniculatus and Mastomys natalensis. Value gained from this research, as well as the current limitations faced when conducting this work are also discussed. Overall, this work helps to shed light on various aspects of these pathogens such as their transmission patterns, pathogenesis (and lack thereof), and mechanisms of persistence in their reservoir hosts. Limitations include a need for highly developed laboratory infrastructure, demanding funding requirements, and a lack of compatible reagents for the exotic species that are often the subject of these studies. Continued interest and research is needed to expand this work to include host reservoirs of other high consequence pathogens so that the risks of future spillover events can be mitigated as best as possible.

The vertical transmission of tomato viruses through seeds and pollen is a significant yet often overlooked pathway for the persistence and global spread of these pathogens. This review provides a comprehensive synthesis of current knowledge on the mechanisms, epidemiological implications, and management strategies of vertically transmitted tomato viruses. While recent advances in diagnostic techniques such as high-throughput sequencing (HTS), have improved virus detection, key research gaps remain in understanding the molecular and ecological dynamics of seed and pollen transmission. The interaction between vertical and horizontal transmission modes complicates virus epidemiology, necessitating an integrated management approach that includes rigorous seed health testing, genetic resistance breeding, and biosecurity measures. Emerging threats, such as resistance-breaking virus strains and the impact of climate change on vector distribution, underscore the need for enhanced surveillance and stronger international regulatory cooperation. This review highlights the need for interdisciplinary research and collaboration to develop sustainable virus mitigation strategies. Future research priorities include optimizing detection methods, exploring next-generation breeding technologies, and strengthening international biosecurity frameworks to safeguard global tomato production against the growing threat of vertically transmitted viruses.

RNA interference (RNAi) is emerging as a powerful technology to potentially protect wheat and barley crops from plant viruses such as Luteovirus pashordei, historicaly known as barley yellow dwarf virus (BYDV), and insect/vector pest infestation. The induction of the RNAi mechanism by the spray on delivery of double-stranded (ds) RNAs that display homology to vital genes encoding virus movement protein, coat protein and other genes related to the virus-plant or virus-vector interaction can lead to limiting virus infection and replication as well as its transmission by aphid vectors. Introducing small interfering RNA (siRNA) into plant cells, targeting these genes, is initiated using various delivery methods, where the most promising is termed spray induced gene silencing (SIGS). This review overviews the significance of barley yellow dwarf viruses (BYDVs) and their aphid vectors. We examine RNAi technology with a focus on the potential for SIGS as a sustainable and environmentally friendly solution for combating barley yellows disease (BYD) in grain crops. The discussion also covers the applications approaches, advantages and disadvantages of this technology, its in-field implementation, the challenges SIGS RNAi application faces and potential for future directions.

Domestic pigs are a vital component of the global food supply, with a population nearing 780 million worldwide, making them one of the most commonly raised livestock. As pig production intensifies, the associated practices and environmental conditions may elevate the risk of emergence and spread of zoonotic agents, including ebolaviruses. Previously, we demonstrated that experimentall infection with Orthoebolavirus bundibugyoense and Orthoebolavirus restonense in pigs caused sub-clinical signs, with only a few animals exhibiting elevated temperatures and limited signs of acute respiratory distress. In this study, we sought to describe immune-related gene exression changes following those viral infections in pigs. Our findings revealed no significant changes in infection- and inflammation-related cytokines, but a strong adaptive immune response was observed in the lungs and tracheobronchial lymph nodes. Comparative analysis with a study in which non-human primates were experimentally infected with Orthoebolavirus bundibugyoense, where the virus is lethal, revealed molecular similarities in gene expression. This may suggest that certain viral processes may be conserved across species. These results highlight the potential role of pigs in ebolavirus spillover dynamics and underscore the importance of understanding the role of livestock in the emergence of these pathogens to guide prevention and mitigation strategies.

Bats are the reservoir hosts for a diverse range of viruses, including some that are highly pathogenic to humans, yet they generally harbor these pathogens without showing symptoms. This unique tolerance to viral infection makes them a critical model to study virus-host interactions and immune responses. Immunological in vivo studies in bats are however often hampered by low reproducibility, a lack of specific reagents, limited access to adequate facilities and availability of inbred bat colonies to perform experiments. In order to overcome these challenges, we have developed a bat xenograft mouse model by intravenously engrafting mice with Rousettus aegyptiacus bone marrow (bat immune system mice; BIS-mice). R. aegyptiacus is of special interest since it is the reservoir host of Marburg virus (MARV). Here we show that MARV does not cause morbidity in bat-engrafted mice, while Ebola virus (EBOV) seems to be highly lethal in this model. Further transcriptome analysis of MARV and EBOV infected BIS-mice revealed that the infection route significantly influences gene expression profiles in host tissues. Additionally, distinct gene expression patterns were observed in BIS-mice when comparing EBOV and MARV infection, underscoring virus-specific timing and intensity of immune gene activation, with MARV typically inducing earlier and more sustained antiviral responses compared to EBOV, which triggers a pronounced inflammatory response. This study demonstrates, for the first time, the use of BIS-mice to study filovirus immunopathogenesis. Additionally, it establishes a crucial foundation for generating bat species-specific immune mouse models, enabling in-depth characterization of bat-borne viruses and promoting translational research in this field.

In response to outbreaks of (re)emerging highly pathogenic RNA viruses, simple and scalable antiviral screening methods are urgently needed. Using established and validated diagnostic methods like RT-PCR for antiviral screening offers a rapid readout of viral replication. This becomes particular important when other traditional viral replication readouts, such as TCID₅₀ or plaque assays cannot be used due to the absence of cytopathic effects, lack of reporter gene-containing recombinant viruses or unavailability of appropriate antibodies - the latter two common challenges when so far unknown viruses emerge. This study evaluated semi-automated diagnostic RT-PCR in a 96-well approach for antiviral compound screening using Marburg virus serving as a case study. Remdesivir, a prodrug that exhibits antiviral activities against multiple RNA viruses, was used as positive control inhibiting replication of filoviruses. Applicability of the protocol to other members of the filovirus family was feasible using the same settings, while for other viruses like Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean-Congo hemorrhagic fever virus (CCHFV) adaptations to optimal infection settings were necessary. Our results demonstrate a high reproducibility and highlight the rapid adaptability of semi-automated RT-PCR assays as an accelerated antiviral screening assay with high scalability against a wide range of newly or (re)emerging RNA viruses. This is critical especially during outbreak situations where timely antiviral assessments are urgently needed.

Plant virus emergence is a major threat for agricultural production and for the preservation of biodiversity in wild ecosystems. This process is determined by genetic and ecological factors and, among the latter, one of the most important is the chance for the virus to encounter susceptible plant populations. Seed transmission has a great potential to facilitate such encounters: from allowing plant viruses to persist locally over unfavorable conditions such as the absence of susceptible hosts, to mediate long range dissemination to reach distant plant populations that could not otherwise be invaded. Here, we review current knowledge on the relationship between plant virus seed transmission and emergence, and on its consequences for the epidemiology of these pathogens. We start by setting up a conceptual framework based on mathematical modelling. Then, we summarize experimental and empirical evidence supporting the central role of seed transmission for initiating damaging plant virus-induced disease epidemics, at different geographical scales and in wild and cultivated plant populations. Finaly, we explore current methodologies to limit the emergence of plant viruses associated with seed transmission. Considering these studies, we propose avenues for future research on this subject.

Zoonotic paramyxoviruses, including the highly pathogenic henipaviruses (HNVs), pose significant risks to global health due to their high mortality rates, potential for human-to-human transmission, and lack of approved countermeasures. Recent metagenomic surveys have uncovered an extensive diversity of HNVs and related paramyxoviruses circulating in wildlife, the majority of which remain uncharacterized due to the dearth of viral isolates. In lieu of viral isolates, reverse genetics systems offer an approach to derive infectious clones de novo in the laboratory, facilitating research into the biology, zoonotic potential, and pathogenicity of novel HNVs. This chapter explores the methodologies and applications of reverse genetics systems for novel HNVs, including considerations for virus sequence validation, full-length virus recovery, and the development of platforms such as minigenomes, replicons, and virus replicon particles. Such biologically-contained life cycle modeling systems enable research to be conducted at lower biocontainment, and provide accessible tools through which to investigate HNV biology. This work demonstrates the versatility of reverse genetics systems in advancing our understanding of high-consequence pathogens, enabling the proactive development of vaccines, antivirals, and diagnostic tools. By integrating these methodologies within a framework of biosafety and biosecurity, researchers can better prepare for and respond to future zoonotic threats.

The Filoviridae family encompasses Ebola virus (EBOV) and Marburg virus (MARV), some of the most lethal viruses known to cause sporadic, recurring outbreaks of severe hemorrhagic fever mainly throughout central Africa. However, other lesser-known viruses also belong to the filovirus family as they are closely related, such as Bundibugyo, Reston and Taï Forest virus. These viruses differ in their virulence in humans significantly: while EBOV and MARV show lethality in humans of up to 90 %, Reston virus appears to be avirulent in humans. Here, underlying molecular factors leading to differences in virulence via changes in filovirus entry, replication and immune evasion strategies are summarized and assessed. While the filovirus glycoprotein contributes towards virulence by facilitating entry into a wide variety of tissues, differences in virus-host interactions and replication efficacies lead to measurable variances of progeny virus production. Additionally, immune evasion strategies lead to alterations in replication efficacy thus changing who has the upper hand between the virus and the host. Understanding and unraveling the contributions of these molecular determinants on filovirus virulence provide insights into the processes causing the underlying pathogenesis. It will further help to assess the pathogenicity of newly discovered filoviruses. Finally, these molecular determinants and processes present attractive targets for therapeutic intervention and development of novel antiviral countermeasures.