BACKGROUND: Metagenomics is a powerful approach for the detection of unknown and novel pathogens. Workflows based on Illumina short-read sequencing are becoming established in diagnostic laboratories. However, high sequencing depth requirements, long turnaround times, and limited sensitivity hinder broader adoption. We investigated whether we could overcome these limitations using protocols based on untargeted sequencing with Oxford Nanopore Technologies (ONT), which offers real-time data acquisition and analysis, or a targeted panel approach, which allows the selective sequencing of known pathogens and could improve sensitivity.
METHODS: We evaluated detection of viruses with readily available untargeted metagenomic workflows using Illumina and ONT, and an Illumina-based enrichment approach using the Twist Bioscience Comprehensive Viral Research Panel (CVRP), which targets 3153 viruses. We tested samples consisting of a dilution series of a six-virus mock community in a human DNA/RNA background, designed to resemble clinical specimens with low microbial abundance and high host content. Protocols were designed to retain the host transcriptome, since this could help confirm the absence of infectious agents. We further compared the performance of commonly used taxonomic classifiers.
RESULTS: Capture with the Twist CVRP increased sensitivity by at least 10-100-fold over untargeted sequencing, making it suitable for the detection of low viral loads (60 genome copies per ml (gc/ml)), but additional methods may be needed in a diagnostic setting to detect untargeted organisms. While untargeted ONT had good sensitivity at high viral loads (60,000 gc/ml), at lower viral loads (600-6000 gc/ml), longer and more costly sequencing runs would be required to achieve sensitivities comparable to the untargeted Illumina protocol. Untargeted ONT provided better specificity than untargeted Illumina sequencing. However, the application of robust thresholds standardized results between taxonomic classifiers. Host gene expression analysis is optimal with untargeted Illumina sequencing but possible with both the CVRP and ONT.
CONCLUSIONS: Metagenomics has the potential to become standard-of-care in diagnostics and is a powerful tool for the discovery of emerging pathogens. Untargeted Illumina and ONT metagenomics and capture with the Twist CVRP have different advantages with respect to sensitivity, specificity, turnaround time and cost, and the optimal method will depend on the clinical context.

Combining different drugs synergistically is an essential aspect of developing effective treatments. Although there is a plethora of research on computational prediction for new combination therapies, there is limited to no research on combination therapies in the treatment of viral diseases. This paper proposes AI-based models for predicting novel antiviral combinations to treat virus diseases synergistically. To do this, we assembled a comprehensive dataset comprising information on viral strains, drug compounds, and their known interactions. As far as we know, this is the first dataset and learning model on combination therapy for viruses. Our proposal includes using a random forest model, an SVM model, and a deep model to train viral combination therapy. The machine learning models showed the highest performance, and the predicted values were validated by a t-test, indicating the effectiveness of the proposed methods. One of the predicted combinations of acyclovir and ribavirin has been experimentally confirmed to have a synergistic antiviral effect against herpes simplex type-1 virus, as described in the literature.

BACKGROUND: Routine screening for viral infections at blood donation is important to avoid transfusion-transmitted infections. It also offers an opportunity to detect an asymptomatic infection.
OBJECTIVE: To study changes in serology positivity for viral infections (B and C hepatitis, HTLV-1/2, and HIV) at blood donation in a blood bank from Southern Brazil, comparing two periods of 5 years: the period from 2013 to 2017 with the period from 2018 to 2022. In addition, data on the donor fidelity rate during the studied period were sought.
METHODS: Retrospective study using data from 2013 to 2022 from a single blood center electronic database from Curitiba, Southern Brazil.
RESULTS: A significant drop in positive serology for all studied viruses was observed: highest in HIV (OR=0.39; 95% CI=0.27-0.57) and lowest in total anti HBc (0.56; 95 CI=0.50-0.63). Anti HBc serology became more commonly seen in women in the period of 2018-2022 when compared to men. No changes in the distribution of positive serology according to donors\' ages were observed. Loyalty rates had a median of 70%, with the lowest being 60% in 2013, while the highest was 73% in 2018 and 2022.
CONCLUSIONS: A significant reduction in discarded blood bags due to viral serology was observed when the period of 2013-2017 was compared to 2018-2022 on this blood bank; the highest reduction was observed in HIV serology and the lowest in HBc serology, which became more common in women in the second period. High rates of donor fidelity were observed during the period studied.

The endoplasmic reticulum (ER) is a unique organelle responsible for protein synthesis and processing, lipid synthesis in eukaryotic cells, and the replication of many animal viruses is closely related to ER. A considerable number of viral proteins are synthesised during viral infection, resulting in the accumulation of unfolded and misfolded proteins in ER, which in turn induces endoplasmic reticulum stress (ERS). ERS further drives three signalling pathways (PERK, IRE1, and ATF6) of the cellular unfolded protein response (UPR) to respond to the ERS. In numerous studies, ERS has been shown to mediate autophagy, a highly conserved cellular degradation mechanism to maintain cellular homeostasis in eukaryotic cells, through the UPR to restore ER homeostasis. ERS-mediated autophagy is closely linked to the occurrence and development of numerous viral diseases in animals. Host cells can inhibit viral replication by regulating ERS-mediated autophagy, restoring the ER\'s normal physiological process. Conversely, many viruses have evolved strategies to exploit ERS-mediated autophagy to achieve immune escape. These strategies include the regulation of PERK-eIF2α-Beclin1, PERK-eIF2α-ATF4-ATG12, IRE1α-JNK-Beclin1, and other signalling pathways, which provide favourable conditions for the replication of animal viruses in host cells. The ERS-mediated autophagy pathway has become a hot topic in animal virological research. This article reviews the most recent research regarding the regulatory functions of ERS-mediated autophagy pathways in animal viral infections, emphasising the underlying mechanisms in the context of different viral infections. Furthermore, it considers the future direction and challenges in the development of ERS-mediated autophagy targeting strategies for combating animal viral diseases, which will contribute to unveiling their pathogenic mechanism from a new perspective and provide a scientific reference for the discovery and development of new antiviral drugs and preventive strategies.

Livestock is a strategic part of the small-farm economy in Southeast Asia\'s society, providing food income, clothing, fertilizer, and draught power. However, incidences or outbreaks of transboundary animal diseases (TADs) are due to converging factors such as the natural hazards\' aftermath, climate change, deforestation, urban growth, changing production conditions, and market chains. Therefore, this affects productivity and impacts farmers\' livelihoods with small holdings. The literature review was carried out to understand the current situation of TADs in Southeast Asia, identifying knowledge gaps to provide actions for disease control and prevention in the region. We have attempted to summarise the scientific literature in English on the prevalence data of TADs in Southeast Asia between 2011 and March 2022. Relatively few studies evaluated the distribution of TAD, where most of the studies focused on diseases that are important for international trade, such as avian influenza (AI), African swine fever (ASF), classical swine fever (CSF), foot-and-mouth disease (FMD) and Newcastle disease (ND). Traditional production systems have received little attention in such studies as they belonged to mainly smallholders. The outbreaks of ASF and lumpy skin disease (LSD) in 2019 resulted in increased research activity between 2019-2022, while the other TADs were ignored in this period. For new emerging TADs diseases such as ASF and LSD, there is only information about the first detection without prevalence information. Therefore, further epidemiological investigations are necessary to reduce the gaps in disease surveillance reporting systems and support the prevention and reduction of further outbreaks.

The recent pandemic caused by the SARS-CoV-2 virus and the associated mental health complications have renewed scholarly interest in the relationship between viral infections and the development of mental illnesses, a topic that was extensively discussed in the previous century in the context of other viruses, such as influenza. The most probable and analyzable mechanism through which viruses influence the onset of mental illnesses is the inflammation they provoke. Both infections and mental illnesses share a common characteristic: an imbalance in inflammatory factors. In this study, we sought to analyze and compare cytokine profiles in individuals infected with viruses and those suffering from mental illnesses. The objective was to determine whether specific viral diseases can increase the risk of specific mental disorders and whether this risk can be predicted based on the cytokine profile of the viral disease. To this end, we reviewed existing literature, constructed cytokine profiles for various mental and viral diseases, and conducted comparative analyses. The collected data indicate that the risk of developing a specific mental illness cannot be determined solely based on cytokine profiles. However, it was observed that the combination of IL-8 and IL-10 is frequently associated with psychotic symptoms. Therefore, to assess the risk of mental disorders in infected patients, it is imperative to consider the type of virus, the mental complications commonly associated with it, the predominant cytokines to evaluate the risk of psychotic symptoms, and additional patient-specific risk factors.

Cytomegalovirus infection contributes to 10-30% of congenital hearing loss in children. Vertebrate peripheral auditory organs include the outer, middle, and inner ear. Their development is regulated by multiple signaling pathways. However, most ear diseases due to viral infections are due to congenital infections and reactivation and affect healthy adults to a lesser extent. This may be due to the fact that viral infections affect signaling pathways that are important for the development of peripheral hearing organs. Therefore, an in-depth understanding of the relationship between viral infections and the signaling pathways involved in the development of peripheral hearing organs is important for the prevention and treatment of ear diseases. In this review, we summarize the effects of viruses on signaling pathways and signaling molecules in the development of peripheral auditory organs.

TRIM proteins are a family of innate immune factors that play diverse roles in innate immunity and protect the cell against viral and bacterial aggression. As part of this special issue on TRIM proteins, we will take advantage of our findings on TRIM69, which acts by reorganizing the microtubules (MTs) in a manner that is fundamentally antiviral, to more generally discuss how host-pathogen interactions that take place for the control of the MT network represent a crucial facet of the struggle that opposes viruses to their cell environment. In this context, we will present several other TRIM proteins that are known to interact with microtubules in situations other than viral infection, and we will discuss evidence that may suggest a possible contribution to viral control. Overall, the present review will highlight the importance that the control of the microtubule network bears in host-pathogen interactions.

The E3 ubiquitin ligase TRIM7 is known to have dual roles during viral infections. Like other TRIM proteins, TRIM7 can regulate the IFN pathway via the regulation of the cytosolic receptors RIG-I or MDA-5, which promote the production of type I interferons (IFN-I) and antiviral immune responses. Alternatively, under certain infectious conditions, TRIM7 can negatively regulate IFN-I signaling, resulting in increased virus replication. A growing body of evidence has also shown that TRIM7 can, in some cases, ubiquitinate viral proteins to promote viral replication and pathogenesis, while in other cases it can promote degradation of viral proteins through the proteasome, reducing virus infection. TRIM7 can also regulate the host inflammatory response and modulate the production of inflammatory cytokines, which can lead to detrimental inflammation. TRIM7 can also protect the host during infection by reducing cellular apoptosis. Here, we discuss the multiple functions of TRIM7 during viral infections and its potential as a therapeutic target.

In recent years, there has been a significant rise in the appearance of new viral infectious diseases among wildlife populations globally [...].