The social lives of viruses and other mobile genetic elements: a commentary on Leeks et al. 2023.

Illustration of life-histories of phages and plasmids through horizontal and vertical transmission (see Figure 1 for more information).

Virus-pathogen interactions improve water quality along the Middle Route of the South-to-North Water Diversion Canal.

Bacterial pathogens and viruses are the leading causes of global waterborne diseases. Here, we discovered an interesting natural paradigm of water "self-purification" through virus-pathogen interactions over a 1432 km continuum along the Middle Route of the South-to-North Water Diversion Canal (MR-SNWDC) in China, the largest water transfer project in the world. Due to the extremely low total phosphorus (TP) content (ND-0.02 mg/L) in the MR-SNWDC, the whole canal has experienced long-lasting phosphorus (P) limitation since its operation in 2015. Based on 4443 metagenome-assembled genomes (MAGs) and 40,261 nonredundant viral operational taxonomic units (vOTUs) derived from our recent monitoring campaign, we found that residential viruses experiencing extreme P constraints had to adopt special adaptive strategies by harboring smaller genomes to minimize nucleotide replication, DNA repair, and posttranslational modification costs. With the decreasing P supply downstream, bacterial pathogens showed repressed environmental fitness and growth potential, and a weakened capacity to maintain P acquisition, membrane formation, and ribonucleotide biosynthesis. Consequently, the unique viral predation effects under P limitation, characterized by enhanced viral lytic infections and an increased abundance of ribonucleotide reductase (RNR) genes linked to viral nuclear DNA replication cycles, led to unexpectedly lower health risks from waterborne bacterial pathogens in the downstream water-receiving areas. These findings highlighted the great potential of water self-purification associated with virus-pathogen dynamics for water-quality improvement and sustainable water resource management.

Burgeoning therapeutic strategies to curb the contemporary surging viral infections.

Significant efforts and initiatives were already made in the health care systems, however in the last few years; our world is facing emergences of viral infections which potentially leading to considerable challenges in terms of higher morbidity, mortality, increased and considerable financial loads on the affected populations. Over ten major epidemics or pandemics have been recorded in the twenty-first century, the ongoing coronavirus pandemic being one of them. Viruses being distinct obligate pathogens largely dependent on living beings are considered as one of the prominent causes of death globally. Although effective vaccines and antivirals have led to the eradication of imperative viral pathogens, the emergences of new viral infections as well as novel drug-resistant strains have necessitated the implementation of ingenious and efficient therapeutic approaches to treat viral outbreaks in the future. Nature being a constant source of tremendous therapeutical resources has inspired us to develop multi-target antiviral drugs, overcoming the challenges and limitations faced by pharmaceutical industry. Recent breakthroughs in the understanding of the cellular and molecular mechanisms of viral reproduction have laid the groundwork for potential treatment approaches including antiviral gene therapy relying on the application of precisely engineered nucleic acids for disabling pathogen replication. The development of RNA interference and advancements in genome manipulating tools have proven to be especially significant in this regard. In this review, we discussed mode of actions and pathophysiological events associated with the viral infections; followed by distributions, and advancement made towards the detection strategies for timely diagnosis. In the later section, current approaches to cope up the viral pathogens and their key limitations have also been elaborated. Lastly, we also explored some novel and potential targets to treat such infections, where attentions were made on next generation gene editing technologies.

Virome comparison (VC): A novel approach to comparing viromes based on virus species specificity and virome specificity diversity.

The human virome, or the viral communities distributed on or in our body, is estimated to contain about 380 trillion of viruses (individuals), which has far reaching influences on our health and diseases. Obviously, the sheer numbers of viruses alone make the comparisons of two or multiple viromes extremely challenging. In fact, the theory of computation in computer science for so-termed NP-hard problems stipulates that the problem is unsolvable when the size of virome is sufficiently large even with fastest supercomputers. Practically, one has to develop heuristic and approximate algorithms to obtain practically satisfactory solutions for NP-hard problems. Here, we extend the species-specificity and specificity-diversity framework to develop a method for virome comparison (VC). The VC method consists of a pair of metrics: virus species specificity (VS) and virome specificity diversity (VSD) and corresponding pair of random search algorithms. Specifically, the VS and VS permutation (VSP) test can detect unique virus species (US) or enriched virus species (ES) in each virome (treatment), and the VSD and VSD permutation (VSDP) test can further determine holistic differences between two viromes or their subsets (assemblages of viruses). The test with four virome data sets demonstrated that the VC method is effective, efficient, and robust.

Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids.

Viruses utilize host lipids to promote the viral life cycle, but much remains unknown as to how this is regulated. Zinc is a critical element for life, and few studies have linked zinc to lipid homeostasis. We demonstrated that Caenorhabditis elegans infection by Orsay virus is dependent upon lipids and that mutation of the master regulator of lipid biosynthesis, sbp-1, reduced Orsay virus RNA levels by ~236-fold. Virus infection could be rescued by dietary supplementation with lipids downstream of fat-6/fat-7. Mutation of a zinc transporter encoded by sur-7, which suppresses the lipid defect of sbp-1, also rescued Orsay virus infection. Furthermore, reducing zinc levels by chemical chelation in the sbp-1 mutant also increased lipids and rescued Orsay virus RNA levels. Finally, increasing zinc levels by dietary supplementation led to an ~1,620-fold reduction in viral RNA. These findings provide insights into the critical interactions between zinc and host lipids necessary for virus infection. IMPORTANCE Orsay virus is the only known natural virus pathogen of Caenorhabditis elegans, which shares many evolutionarily conserved pathways with humans. We leveraged the powerful genetic tractability of C. elegans to characterize a novel interaction between zinc, lipids, and virus infection. Inhibition of the Orsay virus replication in the sbp-1 mutant animals, explained by the lipid depletion, can be rescued by a genetic and pharmacological approach that reduces the zinc accumulation and rescues the lipid levels in this mutant animal. Interestingly, the human ortholog of sbp-1, srebp-1, has been reported to play a role for virus infection, and zinc has been shown to inhibit the virus replication of multiple viruses. However, the mechanism through which zinc is acting is not well understood. These results suggest that the lipid regulation mediated by zinc may play a relevant role during mammalian virus infection.

The pollen virome of wild plants and its association with variation in floral traits and land use.

Pollen is a unique vehicle for viral spread. Pollen-associated viruses hitchhike on or within pollen grains and are transported to other plants by pollinators. They are deposited on flowers and have a direct pathway into the plant and next generation via seeds. To discover the diversity of pollen-associated viruses and identify contributing landscape and floral features, we perform a species-level metagenomic survey of pollen from wild, visually asymptomatic plants, located in one of four regions in the United States of America varying in land use. We identify many known and novel pollen-associated viruses, half belonging to the Bromoviridae, Partitiviridae, and Secoviridae viral families, but many families are represented. Across the regions, species harbor more viruses when surrounded by less natural and more human-modified environments than the reverse, but we note that other region-level differences may also covary with this. When examining the novel connection between virus richness and floral traits, we find that species with multiple, bilaterally symmetric flowers and smaller, spikier pollen harbored more viruses than those with opposite traits. The association of viral diversity with floral traits highlights the need to incorporate plant-pollinator interactions as a driver of pollen-associated virus transport into the study of plant-viral interactions.

phoH-carrying virus communities responded to multiple factors and their correlation network with prokaryotes in sediments along Bohai Sea, Yellow Sea, and East China Sea in China.

Viruses carrying phoH genes are an important functional group that may boost phosphate metabolism of their prokaryote hosts and affect phosphorus cycle in the ocean. However, at present, very little is known about the phoH-carrying viruses' community structure and diversity in marine sediments, as well as their correlation network with prokaryotes and environment. Here, via a large spatial scale investigation along the Bohai Sea, Yellow Sea, and East China Sea, for the first time, diverse unknown benthic phoH-carrying viruses were uncovered, which were mainly affiliated to three clusters. Interestingly, these viruses presented a very distinct community structure compared to those in seawaters. Correlation network analysis implied that these viruses might mainly infect the prokaryotes of Gamm-/Delta-proteobacteria, Thaumarchaeota, and Cyanobacteria in sediments. Distinct virus-prokaryote correlation network modules were shown in different sea areas. These modules' highly nested feature implied their coevolution with prokaryotes during long-term arms race. Their distribution in sediments was influenced by multiple factors including geographic separation and the key environmental variables of total organic carbon and total phosphorus, and responded to terrestrial inputs and coastal aquaculture activities. The results of this study provide novel insights into the benthic virus communities potentially participating in phosphorus cycling in the ocean.

Viruses of the oral cavity: Prevalence, pathobiology and association with oral diseases.

The human oral cavity contains a plethora of habitats and tissue environments, such as teeth, tongue, and gingiva, which are home to a rich microbial flora including bacteria, fungi, and viruses. Given the exposed nature of the mouth, oral tissues constantly encounter infectious agents, forming a complex ecological community. In the past, the discussion of microbiological aspects of oral disease has traditionally focused on bacteria and fungi, but viruses are attracting increasing attention as pathogens in oral inflammatory diseases. Therefore, understanding viral prevalence, pathogenicity, and preference regarding oral tissues is critical to understanding the holistic effects of viruses on oral infections. Recent investigations have demonstrated the abundance of certain viruses in oral inflammatory diseases, suggesting an association between viruses and disease. Human herpesviruses are the most extensively studied viruses in different oral inflammatory diseases. However, challenges in viral detection and the lack of reproducible in vitro and in vivo infection models have limited our progress in understanding viruses and their contribution to oral diseases. This review presents a summary of major mammalian viruses and associated diseases in the human oral cavity. The emergence of a recent pathogen SARS-CoV-2 and its tropism for salivary and periodontal tissues further highlights the relevance of the oral cavity in host-pathogen interaction. Understanding how these different viruses present clinically and influence oral health will advance our understanding of multifactorial oral diseases and their association with viruses.

Prokaryotic viruses impact functional microorganisms in nutrient removal and carbon cycle in wastewater treatment plants.

As one of the largest biotechnological applications, activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses, with 10-1,000-fold higher concentrations than in natural environments. However, the compositional variation and host-connections of AS viruses remain poorly explored. Here, we report a catalogue of ~50,000 prokaryotic viruses from six WWTPs, increasing the number of described viral species of AS by 23-fold, and showing the very high viral diversity which is largely unknown (98.4-99.6% of total viral contigs). Most viral genera are represented in more than one AS system with 53 identified across all. Viral infection widely spans 8 archaeal and 58 bacterial phyla, linking viruses with aerobic/anaerobic heterotrophs, and other functional microorganisms controlling nitrogen/phosphorous removal. Notably, Mycobacterium, notorious for causing AS foaming, is associated with 402 viral genera. Our findings expand the current AS virus catalogue and provide reference for the phage treatment to control undesired microorganisms in WWTPs.

Tracing the fate of wastewater viruses reveals catchment-scale virome diversity and connectivity.

The discharge of wastewater-derived viruses in aquatic environments impacts catchment-scale virome composition. To explore this, we used viromic analysis of RNA and DNA virus-like particles to holistically track virus communities entering and leaving wastewater treatment plants and the connecting river catchment system and estuary. We reconstructed >40 000 partial viral genomes into 10 149 species-level groups, dominated by dsDNA and (+)ssRNA bacteriophages (Caudoviricetes and Leviviricetes) and a small number of genomes that could pose a risk to human health. We found substantial viral diversity and geographically distinct virus communities associated with different wastewater treatment plants. River and estuarine water bodies harboured more diverse viral communities in downstream locations, influenced by tidal movement and proximity to wastewater treatment plants. Shellfish and beach sand were enriched in viral communities when compared with the surrounding water, acting as entrapment matrices for virus particles. Extensive phylogenetic analyses of environmental-derived and reference sequences showed the presence of human-associated sapovirus GII in all sample types, multiple rotavirus A strains in wastewater and a diverse set of picorna-like viruses associated with shellfish. We conclude that wastewater-derived viral genetic material is commonly deposited in the environment and can be traced throughout the freshwater-marine continuum of the river catchment, where it is influenced by local geography, weather events and tidal effects. Our data illustrate the utility of viromic analyses for wastewater- and environment-based ecology and epidemiology, and we present a conceptual model for the circulation of all types of viruses in a freshwater catchment.

DescribePROT: database of amino acid-level protein structure and function predictions.

We present DescribePROT, the database of predicted amino acid-level descriptors of structure and function of proteins. DescribePROT delivers a comprehensive collection of 13 complementary descriptors predicted using 10 popular and accurate algorithms for 83 complete proteomes that cover key model organisms. The current version includes 7.8 billion predictions for close to 600 million amino acids in 1.4 million proteins. The descriptors encompass sequence conservation, position specific scoring matrix, secondary structure, solvent accessibility, intrinsic disorder, disordered linkers, signal peptides, MoRFs and interactions with proteins, DNA and RNAs. Users can search DescribePROT by the amino acid sequence and the UniProt accession number and entry name. The pre-computed results are made available instantaneously. The predictions can be accesses via an interactive graphical interface that allows simultaneous analysis of multiple descriptors and can be also downloaded in structured formats at the protein, proteome and whole database scale. The putative annotations included by DescriPROT are useful for a broad range of studies, including: investigations of protein function, applied projects focusing on therapeutics and diseases, and in the development of predictors for other protein sequence descriptors. Future releases will expand the coverage of DescribePROT. DescribePROT can be accessed at http://biomine.cs.vcu.edu/servers/DESCRIBEPROT/.

Detection of Enteric Viruses and Bacterial Indicators in a Sewage Treatment Center and Shallow Water Bay.

The incidence of enteric viruses in treated wastewater and their potential release into the environment or use for agriculture are very critical matters in public health. In our study, PCR (polymerase chain reaction) analysis of enteric viruses was performed on 59 samples of influents and effluents collected from Tubli wastewater treatment plant (Water Pollution Control Center (WPCC)) and Tubli Bay, where the effluents were discharged, in Kingdom of Bahrain during two sampling periods. Four clinically essential waterborne enteric viruses were examined: enterovirus (EV), hepatitis A virus (HAV), astroviruses (AV), and rotaviruses (RV) and compared to standard bacterial and bacteriophages indicators of fecal pollution. Detection rates of EV, AV, HAV, and RV in the influent samples were 100%, 75%, 12.5%, and 12.5%, respectively, while 50% of the effluent samples from Tubli WPCC contained only EV RNA. None of the tested enteric viruses could be detected in any of the samples collected directly from Tubli Bay. Effluent samples from Tubli plant did not show significant seasonal differences. Since detection of enteric viruses genome does not necessarily indicate infectivity, the infectivity of these viruses was evaluated through isolation and growth of indictor bacteria and bacteriophages. High concentration of fecal bacteriological indicators was detected in all effluents samples (100%): 3.20 × 103 cfu/mL for E. coli, 1.32 × 103 cfu/mL for Salmonella spp., and 1.92 × 103 cfu/mL for Shigella spp. E. coli and Salmonella specific bacteriophages were also detected in the effluent samples in high titers. The combined results of PCR and bacterial enumeration point to a probable public health risk via the use of these wastewaters in agriculture or their discharge into the sea. Continuous surveillance of viral and bacterial prevalence and their resistance to sewage disinfection procedures could contribute to a better control of risks associated with the recycling of effluent wastewater and its release into the environment.

Antiviral activity of berberine.

Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.

Multifaceted Functions of Host Cell Caveolae/Caveolin-1 in Virus Infections.

Virus infection has drawn extensive attention since it causes serious or even deadly diseases, consequently inducing a series of social and public health problems. Caveolin-1 is the most important structural protein of caveolae, a membrane invagination widely known for its role in endocytosis and subsequent cytoplasmic transportation. Caveolae/caveolin-1 is tightly associated with a wide range of biological processes, including cholesterol homeostasis, cell mechano-sensing, tumorigenesis, and signal transduction. Intriguingly, the versatile roles of caveolae/caveolin-1 in virus infections have increasingly been appreciated. Over the past few decades, more and more viruses have been identified to invade host cells via caveolae-mediated endocytosis, although other known pathways have been explored. The subsequent post-entry events, including trafficking, replication, assembly, and egress of a large number of viruses, are caveolae/caveolin-1-dependent. Deprivation of caveolae/caveolin-1 by drug application or gene editing leads to abnormalities in viral uptake, viral protein expression, or virion release, whereas the underlying mechanisms remain elusive and must be explored holistically to provide potential novel antiviral targets and strategies. This review recapitulates our current knowledge on how caveolae/caveolin-1 functions in every step of the viral infection cycle and various relevant signaling pathways, hoping to provide a new perspective for future viral cell biology research.

Interspecies cross-feeding orchestrates carbon degradation in the rumen ecosystem.

Because of their agricultural value, there is a great body of research dedicated to understanding the microorganisms responsible for rumen carbon degradation. However, we lack a holistic view of the microbial food web responsible for carbon processing in this ecosystem. Here, we sampled rumen-fistulated moose, allowing access to rumen microbial communities actively degrading woody plant biomass in real time. We resolved 1,193 viral contigs and 77 unique, near-complete microbial metagenome-assembled genomes, many of which lacked previous metabolic insights. Plant-derived metabolites were measured with NMR and carbohydrate microarrays to quantify the carbon nutrient landscape. Network analyses directly linked measured metabolites to expressed proteins from these unique metagenome-assembled genomes, revealing a genome-resolved three-tiered carbohydrate-fuelled trophic system. This provided a glimpse into microbial specialization into functional guilds defined by specific metabolites. To validate our proteomic inferences, the catalytic activity of a polysaccharide utilization locus from a highly connected metabolic hub genome was confirmed using heterologous gene expression. Viral detected proteins and linkages to microbial hosts demonstrated that phage are active controllers of rumen ecosystem function. Our findings elucidate the microbial and viral members, as well as their metabolic interdependencies, that support in situ carbon degradation in the rumen ecosystem.

White paper on microbial anti-cancer therapy and prevention.

In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting ('Microbial Based Cancer Therapy') at the US National Cancer Institute in the summer of 2017. Here, we define 'Microbial Therapy' to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care.

Matrix approach to the simultaneous detection of multiple potato pathogens by real-time PCR.

AIM: Create a method for highly sensitive, selective, rapid and easy-to-use detection and identification of economically significant potato pathogens, including viruses, bacteria and oomycetes, be it single pathogen, or a range of various pathogens occurring simultaneously. METHODS AND RESULTS: Test-systems for real-time PCR, operating in the unified amplification regime, have been developed for Phytophthora infestans, Pectobacterium atrosepticum, Dickeya dianthicola, Dickeya solani, Ralstonia solanacearum, Pectobacterium carotovorum, Clavibacter michiganensis subsp. sepedonicus, potato viruses Y (ordinary and necrotic forms as well as indiscriminative test system, detecting all forms), A, X, S, M, potato leaf roll virus, potato mop top virus and potato spindle tuber viroid. The test-systems (including polymerase and revertase) were immobilized and lyophilized in miniature microreactors (1·2 µl) on silicon DNA/RNA microarrays (micromatrices) to be used with a mobile AriaDNA® amplifier. CONCLUSIONS: Preloaded 30-reaction micromatrices having shelf life of 3 and 6 months (for RNA- and DNA-based pathogens, respectively) at room temperature with no special conditions were successfully tested on both reference and field samples in comparison with traditional ELISA and microbiological methods, showing perfect performance and sensitivity (1 pg). SIGNIFICANCE AND IMPACT OF THE STUDY: The accurate, rapid and user-friendly diagnostic system in a micromatrix format may significantly contribute to pathogen screening and phytopathological studies.

Neural systems mediating the inhibition of cocaine-seeking behaviors.

Over the past decades, research has targeted the neurobiology regulating cocaine-seeking behaviors, largely in the hopes of identifying potential targets for the treatment of cocaine addiction. Although much of this work has focused on those systems driving cocaine seeking, recently, studies examining the inhibition of cocaine-related behaviors have made significant progress in uncovering the neural systems that attenuate cocaine seeking. Such systems include the infralimbic cortex, nucleus accumbens shell, and hypothalamus. Research in this field has focused largely on the infralimbic cortex, as activity in this region appears to attenuate cocaine seeking during reinstatement and contribute to extinction learning. However, an overarching theory of function for this region that includes its role in other types of reward seeking and learning remains to be determined. Furthermore, the precise relationship between other regions involved in attenuating cocaine-seeking behavior and the infralimbic cortex remains unclear. Recent advances in the use of viral vectors combined with optogenetics, chemogenetics, and other approaches have greatly affected our capacity to investigate those systems inhibiting behavior dependent on cocaine-associated memories. This review will present current understanding regarding the neurobiology underlying the inhibition of such behaviors, especially focusing on the extinction of such memories, and explore how viral-vector targeting of specific brain circuits has begun to alter, and will continue to enrich, our knowledge regarding this issue.

Ecology of the Oral Microbiome: Beyond Bacteria.

Although great strides have been made in understanding the complex bacterial community inhabiting the human oral cavity, for a variety of (mainly technical) reasons the ecological contributions of oral fungi, viruses, phages, and the candidate phyla radiation (CPR) group of ultrasmall bacteria have remained understudied. Several recent reports have illustrated the diversity and importance of these organisms in the oral cavity, while TM7x and Candida albicans have served as crucial paradigms for CPR species and oral fungi, respectively. A comprehensive understanding of the oral microbiota and its influence on host health and disease will require a holistic view that emphasizes interactions among different residents within the oral community, as well as their interaction with the host.