Related Viruses Research Articles

An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses.

The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well-conserved among sarbecoviruses, but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

Defining virus-carrier networks that shape the composition of the mosquito core virome of a local ecosystem.

Mosquitoes are the most important vectors of emerging infectious diseases. During the past decade, our understanding of the diversity of viruses they carry has greatly expanded. Most of these viruses are considered mosquito-specific, but there is increasing evidence that these viruses may affect the vector competence of mosquitoes. Metagenomics approaches have focused on specific mosquito species for the identification of what is called the core virome. Despite the fact that, in most ecosystems, multiple species may participate in virus emergence and circulation, there is a lack of understanding of the virus-carrier/host network for both vector-borne and mosquito-specific viruses. Here, we studied the core virome of mosquitoes in a diverse local ecosystem that had 24 different mosquito species. The analysis of the viromes of these 24 mosquito species resulted in the identification of 34 viruses, which included 15 novel viruses, as determined according to the species demarcation criteria of the respective virus families. Most of the mosquito species had never been analysed previously, and a comparison of the individual viromes of the 24 mosquito species revealed novel relationships among mosquito species and virus families. Groups of related viruses and mosquito species from multiple genera formed a complex web in the local ecosystem. Furthermore, analyses of the virome of mixed-species pools of mosquitoes from representative traps of the local ecosystem showed almost complete overlap with the individual-species viromes identified in the study. Quantitative analysis of viruses’ relative abundance revealed a linear relationship to the abundance of the respective carrier/host mosquito species, supporting the theory of a stable core virome in the most abundant species of the local ecosystem. Finally, our study highlights the importance of using a holistic approach to investigating mosquito viromes relationships in rich and diverse ecosystems.

MiR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos.

BackgroundWe aimed to investigate the effects of miR-34a-5p on c-fos regulation mediating the malignant behaviors of SH-SY5Y cells infected with Kaposi’s sarcoma-associated herpesvirus (KSHV).MethodsThe KSHV-infected (SK-RG) and uninfected SH-SY5Y parent cells were compared for differentially expressed miRNAs using transcriptome sequencing. Then miR-34a-5p was upregulated in SK-RG cells by the miRNA mimics transfection. Cell proliferation ability was determined by MTT and plate clone assays. The cell cycle was assessed by flow cytometry analysis, and CDK4, CDK6, cyclin D1 levels were determined by Western blot analysis. The migration behavior was detected by wound healing and transwell assays. The protein levels of MMP2 and MMP9 were measured by Western blot analysis. The regulation of c-fos by miR-34a-5p was detected by the dual-luciferase reporter gene assay. Rescue assays were carried out by upregulating c-fos in miR-34a-5p-overexpressing SK-RG cells. KSHV DNA copy numbers and relative virus gene expressions were detected. Xenograft tumor experiments and immunohistochemistry assays were further used to detect the effects of miR-34a-5p.ResultsmiR-34a-5p was lower in SK-RG cells. Restoration of miR-34a-5p decreased cell proliferation and migration, leading to a G1 cell cycle arrest and down-regulation of CDK4/6, cyclin D1, MMP2, MMP9. KSHV copy number and expression of virus gene including latency-associated nuclear antigen (LANA), replication and transcription activator (RTA), open reading frame (K8.1), and KSHV G protein-coupled receptor (v-GPCR) were also reduced. Furthermore, c-fos is the target of miR-34a-5p, while enhanced c-fos weakened cellular behaviors of miR-34a-5p-overexpressing cells. Xenograft experiments and immunohistochemistry assays showed that miR-34a-5p inhibited tumor growth and virus gene expression.ConclusionUpregulated miR-34a-5p in KSHV-infected SH-SY5Y cells suppressed cell proliferation and migration through down-regulating c-fos. miR-34a-5p was a candidate molecular drug for KSHV-infected neuronal cells.

Bovine Herpesvirus 1 Invasion of Sensory Neurons by Retrograde Axonal Transport Is Dependent on the pUL37 Region 2 Effector.

Following exposure and replication at mucosal surfaces, most alphaherpesviruses invade the peripheral nervous system by retrograde axonal transport and establish lifelong latent infections in the peripheral ganglia. Reactivation of ganglionic infections is followed by anterograde axonal transport of virions back to body surfaces where viral replication results in disease that can range from moderate to severe in presentation. In the case of bovine herpesvirus 1 (BoHV-1), replication in the epithelial mucosa presents as infectious bovine rhinotracheitis (IBR), a respiratory disease of significant economic impact. In this study, we provide a live-cell analysis of BoHV-1 retrograde axonal transport relative to the model alphaherpesvirus pathogen pseudorabies virus (PRV) and demonstrate that this critical neuroinvasive step is conserved between the two viruses. In addition, we report that the BoHV-1 pUL37 tegument protein supports processive retrograde motion in infected axons and invasion of the calf peripheral nervous system. IMPORTANCE A molecular and cellular understanding of the retrograde axonal transport process that underlies the neuroinvasive properties of the alphaherpesviruses is established from studies of herpes simplex virus and pseudorabies virus. The degree to which this phenotype is conserved in other related viruses has largely not been examined. We provide a time-lapse analysis of the retrograde axonal transport kinetics of bovine herpesvirus 1 and demonstrate that mutation of the pUL37 region 2 effector affords a strategy to produce live-attenuated vaccines for enhanced protection of cattle.

Identification and Validation of Quantitative Trait Loci for Wheat Dwarf Virus Resistance in Wheat (Triticum spp.).

Wheat dwarf virus (WDV) is transmitted by the leafhopper Psammotettix alienus. As a major pathogen in wheat and other cereals, WDV causes high yield losses in many European countries. Due to climate change, insect-transmitted viruses will become more important and the restrictions in the use of insecticides efficient against P. alienus renders growing of WDV resistant/tolerant varieties the only effective strategy to control WDV. So far, there is little information about the possible sources of resistance and no known information about the genome regions responsible for the resistance. In a screening for WDV resistance using artificial inoculation in gauze houses, a panel of 500 wheat accessions including cultivars, gene bank accessions, and wild relatives of wheat was phenotyped for virus titer, infection rate, as well as plant height and yield parameters relative to healthy controls of the same genotype. Additionally, 85 T. aestivum-Ae. tauschii intogression lines were tested for WDV resistance in the greenhouse. A subset of 250 hexaploid wheat accessions was genotyped with the 15k iSelect SNP Chip. By genome-wide association study (GWAS), the quantitative trait loci (QTL) for partial WDV resistance were identified. Within these studies, one cultivar was identified showing an average infection rate of only 5.7%. By analyzing single seed descent (SSD) and doubled haploid (DH) populations comprising 153 and 314 individuals for WDV resistance and by genotyping these with the 25k iSelect SNP Chip, QTL for yield per plant, thousand-grain weight, and relative virus titer were validated on chromosomes 1B, 2B, 3B, 4B, 4A, 5A, 6A, and 7A. These results will be the basis for marker-assisted selection for WDV resistance to replacing the laborious, time-consuming, and technically challenging phenotyping with WDV bearing leafhoppers.

Neuronal miR-138 Represses HSV-2 Lytic Infection by Regulating Viral and Host Genes with Mechanistic Differences from HSV-1.

Herpes simplex virus 2 (HSV-2) establishes latent infection in dorsal root ganglion (DRG) neurons after productive (lytic) infection in peripheral tissues. A neuron-specific microRNA, miR-138, favors HSV-1 latency by repressing viral ICP0 and host Oct-1 and Foxc1 genes, yet the role of miR-138 in HSV-2 infection was unknown. The ICP0 mRNAs of HSV-1, HSV-2, and chimpanzee herpesvirus each have one to two canonical miR-138 binding sites. The sites are 100% conserved in 308 HSV-1 and 300 HSV-2 published sequences of clinical isolates. In cotransfection assays, miR-138 repressed HSV-2 ICP0 expression through the seed region and surrounding interactions that are different from HSV-1. An HSV-2 mutant with disrupted miR-138 binding sites on ICP0 showed increased ICP0 expression in Neuro-2a cells. Photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation confirmed miR-138 binding to HSV-2 ICP0 and identified UL19 and UL20 as additional targets whose expression was repressed by miR-138 during cotransfection. In Neuro-2a cells, transfected miR-138 and its antagomir decreased and increased HSV-2 replication, respectively, and a knockout experiment showed that miR-138's host targets OCT-1 and FOXC1 were important for HSV-2 replication. In primary mouse DRG neurons, both ICP0 and FOXC1 positively regulated HSV-2 replication, but both overexpressed and endogenous miR-138 suppressed HSV-2 replication primarily by repressing ICP0 expression. Thus, miR-138 can suppress HSV-2 neuronal replication through multiple viral and host pathways. These results reveal functional similarities and mechanistic differences in how miR-138 regulates HSV-1 and HSV-2 infection and indicate an evolutionary advantage of using miR-138 to repress lytic infection in neurons. IMPORTANCE HSV-1 and HSV-2 are closely related viruses with major differences. Both viruses establish latency in neurons from which they reactivate to cause disease. A key aspect of HSV latency is repression of productive infection in neurons. Based on previous work with HSV-1, we investigated the role of a neuron-specific microRNA, miR-138, in HSV-2 infection and established it as a repressor of HSV-2 productive infection in neuronal cells. This repression is mediated mainly by targeting viral ICP0 and host Foxc1 mRNAs, but other pathways also contribute. Despite functional conservation of the role of miR-138 between HSV-1 and HSV-2, many molecular mechanisms differ, including how miR-138 represses ICP0 expression and miR-138 targeting of HSV-2 but not HSV-1 UL19 and UL20. To our knowledge, this study provides the first example of host microRNA regulation of HSV-2 infection.

Picorna-Like Viruses of the Havel River, Germany.

To improve the understanding of the virome diversity of riverine ecosystems in metropolitan areas, a metagenome analysis was performed with water collected in June 2018 from the river Havel in Berlin, Germany. After enrichment of virus particles and RNA extraction, paired-end Illumina sequencing was conducted and assignment to virus groups and families was performed. This paper focuses on picorna-like viruses, the most diverse and abundant group of viruses with impact on human, animal, and environmental health. Here, we describe altogether 166 viral sequences ranging in size from 1 to 11.5 kb. The 71 almost complete genomes are comprised of one candidate iflavirus, one picornavirus, two polycipiviruses, 27 marnaviruses, 27 dicistro-like viruses, and 13 untypeable viruses. Many partial picorna-like virus sequences up to 10.2 kb were also investigated. The sequences of the Havel picorna-like viruses represent genomes of seven of eight so far known Picornavirales families. Detection of numerous distantly related dicistroviruses suggests the existence of additional, yet unexplored virus groups with dicistronic genomes, including few viruses with unusual genome layout. Of special interest is a clade of dicistronic viruses with capsid protein-encoding sequences at the 5′-end of the genome. Also, monocistronic viruses with similarity of their polymerase and capsid proteins to those of dicistroviruses are interesting. A second protein with NTP-binding site present in the polyprotein of solinviviruses and related viruses needs further attention. The results underline the importance to study the viromes of fluvial ecosystems. So far acknowledged marnaviruses have been isolated from marine organisms. However, the present study and available sequence data suggest that rivers and limnic habitats are relevant ecosystems with circulation of marnaviruses as well as a plethora of unknown picorna-like viruses.

Development of a Reverse Transcription Loop - Mediated Isothermal Amplification [RT-LAMP] as a early rapid detection assay for Crimean Congo Hemorrhagic Fever virus

Presently diagnosis of Crimean Congo Hemorrhagic Fever virus (CCHFV) infection relies on real-time and end-point RT-PCR, and serodiagnostic assay. These assays are time consuming and cannot be used as a routine screening test. The objective of this study was to develop a rapid diagnostic test that could be completed in < 60 minutes. Rapid detection of CCHFV infection is important for faster delivery of appropriate therapeutics, clinical management of patient and also important to contain the outbreak. In the present study, we have developed a rapid and sensitive single tube reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of CCHFV. The limit of detection of RT-LAMP vis-a-vis Real-time RT-PCR assay is 10 RNA copies. Further, CCHFV specific RT-LAMP assay was successfully evaluated with human and tick samples. The assay correctly picked up diverse CCHFV isolates indicating its applicability for different strains. A comparative evaluation of the RT-LAMP assay vis-à-vis with the real-time RT-PCR revealed 100% concordance with 100 % sensitivity and specificity respectively. No cross reactivity with related Flaviviruses and hemorrhagic fever viruses was observed. The assay is a rapid, isothermal, simple to perform molecular diagnostic, which can be performed in a portable heating block device. CCHF RT-LAMP assay can be used in low resource laboratories for monitoring of CCHFV outbreaks in remote rural regions in affected countries.

Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies due to structural and dynamic changes of the viral spike glycoprotein (S). The heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of S drive virus–host membrane fusion by assembly into a six-helix bundle, resulting in delivery of viral RNA into the host cell. We surveyed mutations of currently reported SARS-CoV-2 variants and selected eight mutations, including Q954H, N969K, and L981F from the Omicron variant, in the postfusion HR1HR2 bundle for functional and structural studies. We designed a molecular scaffold to determine cryogenic electron microscopy (cryo-EM) structures of HR1HR2 at 2.2–3.8 Å resolution by linking the trimeric N termini of four HR1 fragments to four trimeric C termini of the Dps4 dodecamer from Nostoc punctiforme. This molecular scaffold enables efficient sample preparation and structure determination of the HR1HR2 bundle and its mutants by single-particle cryo-EM. Our structure of the wild-type HR1HR2 bundle resolves uncertainties in previously determined structures. The mutant structures reveal side-chain positions of the mutations and their primarily local effects on the interactions between HR1 and HR2. These mutations do not alter the global architecture of the postfusion HR1HR2 bundle, suggesting that the interfaces between HR1 and HR2 are good targets for developing antiviral inhibitors that should be efficacious against all known variants of SARS-CoV-2 to date. We also note that this work paves the way for similar studies in more distantly related viruses.

Detection of Quaranjavirus-Like Sequences from Haemaphysalis hystricis Ticks Collected in Japan.

Viruses belonging to the genus Quaranjavirus in the family Orthomyxoviridae are known as argasid tick-borne viruses. Some viruses in this genus or an unassigned quaranjavirus-like variant can infect humans, although little is known about their pathogenicity. During the surveillance of tick-borne viruses in ixodid ticks in Ehime Prefecture, Japan, novel quaranjavirus-like sequences were detected in 3 pooled samples of Haemaphysalis histricis nymphs. Phylogenetic analysis revealed that the detected viruses formed a cluster with quaranjaviruses and other related viruses. Specifically, the viruses were closely related to Zambezi tick virus 1 and Uumaja virus, which are quaranjavirus-like viruses recently discovered in ixodid ticks in Africa and Europe, respectively. These findings indicate that the viruses detected in this study were probably new members of the Quaranjavirus genus or a related group. The viruses were tentatively named "Ohshima virus" even though only limited sequences of their genomes were available. This is the first report on the detection of a quaranjavirus-like virus in the East Asian region. Further investigations are needed to discern its infectivity and pathogenicity against humans and other animals and to determine the potential risk of an emerging tick-borne viral disease.

The calcium channel inhibitor lacidipine inhibits Zika virus replication in neural progenitor cells

After decades of being considered non-pathogenic, Zika virus (ZIKV) emerged as an important threat to human health during the epidemic of 2015–2016. ZIKV infections are usually asymptomatic, but can cause Guillain-Barré syndrome in adults and microcephaly in newborns. As there are currently no approved antiviral drugs against ZIKV, we tested anti-ZIKV activity of compounds from the NIH Clinical Collection for which we previously showed antiviral activity against the related dengue virus. One of the top hits from the screen was lacidipine, a 1,4-dihydropyridine calcium antagonist that is approved as an antihypertensive drug. Our data show that lacidipine is antiviral against ZIKV (strain H/PF/2013) in both Vero cells and induced pluripotent stem cell (iPSC)-derived human neural progenitor cells with IC50 values of 3.0 μM and <50 nM, respectively. The antiviral effect was also observed against four other ZIKV strains from the African and Asian lineages. Time-of-addition and replicon assays indicated that lacidipine acts at the post-entry stage of the viral replication cycle, inhibiting viral genome replication. Lacidipine altered the subcellular distribution of free cholesterol and neutral lipids, suggesting that the antiviral effect of lacidipine is mediated by altered trafficking of lipids. Together, these results identify lacidipine as a novel inhibitor of ZIKV replication that likely disturbs trafficking of lipids needed for replication organelle formation.

Different Detection Methods of Blood Nucleic Acid and Enzyme-linked Immunosorbent Assay for Blood Virus Screening

Through the detection of antigens or antibodies of related viruses in blood, the incidence of transfusion-transmitted diseases can be reduced, the comprehensive performance indicators of the human body can be judged, and the disease can be effectively treated and prevented. The purpose of this study is to analyze the screening results of blood viruses by different detection methods of blood nucleic acid and enzyme-linked immunosorbent assay. In this study, the comparison and data analysis of the two detection methods in the study were carried out through the comparison method and data analysis method, and the functional analysis is combined with the detection principle. The positive rate of anti-HCV was 1.67% (10 / 600) by ELISA and 0.34% (2 / 590) by nucleic acid. Conclusion enzyme immunoassay is not sensitive to the antigen-antibody reaction in the window stage, and there is a mistake in the detection. However, nucleic acid detection has high sensitivity because of its PCR principle, but it is also prone to false-positive.

Review] Coronaviruses in Wild Canids: A review of the literature

The Coronaviridae is a ubiquitous viral family, capable of causing disease in domestic and wildlife species, in addition to substantial human disease as indicated by the SARS-CoV-2 pandemic. The spillover of SARS-CoV-2 into wildlife and domestic species is an ongoing concern for both conservation and public health. Following the 2002 SARS-CoV outbreak, surveillance identified a related virus in raccoon dogs that was considered a potential intermediate host between infection in bats and humans. Two other coronaviruses circulate widely in domestic dogs: namely canine coronavirus (CCoV) and canine respiratory coronavirus, and may be transmitted to and amongst wild canids. Domestic dogs have also been identified as an infrequent host for SARS-CoV-2. The spillover of CCoV has been investigated in numerous wild canid populations, primarily using serology. Here, we review reports of coronaviruses in wild canids, helping provide a baseline for future disease surveillance.

One Health and Cattle Genetic Resources: Mining More than 500 Cattle Genomes to Identify Variants in Candidate Genes Potentially Affecting Coronavirus Infections.

Simple SummaryThe conservation and exploitation of cattle genetic resources for selection and breeding purposes are important for the definition of sustainable livestock production sectors. One Health approaches should be integrated into these activities to reduce the risk posed by many zoonoses. Coronaviruses are emerging as important zoonotic agents, with the potential to easily cross species barriers, as also recently demonstrated by the COVID-19 pandemic derived by SARS-CoV-2. Genetic resistance to coronavirus infections can be determined by variants of the host (animal) genome segregating within species. In this study, we mined the genome of more than 500 cattle to identify variants that could be involved so as to define different levels of susceptibility and/or resistance to coronavirus diseases in this important livestock species. Using comparative analyses across species, we identified several single amino acid polymorphisms that might alter the function of key proteins involved in the basic biological mechanisms underlying the infection processes in cattle. This study provided new elements to consider genetic variability of the host (cattle) as a potential risk factor to be considered in One Health perspectives.Epidemiological and biological characteristics of coronaviruses and their ability to cross species barriers are a matter of increasing concerns for these zoonotic agents. To prevent their spread, One Health approaches should be designed to include the host (animal) genome variability as a potential risk factor that might confer genetic resistance or susceptibility to coronavirus infections. At present, there is no example that considers cattle genetic resources for this purpose. In this study, we investigated the variability of six genes (ACE2, ANPEP, CEACAM1 and DPP4 encoding for host receptors of coronaviruses; FURIN and TMPRSS2 encoding for host proteases involved in coronavirus infection) by mining whole genome sequencing datasets from more than 500 cattle of 34 Bos taurus breeds and three related species. We identified a total of 180 protein variants (44 already known from the ARS-UCD1.2 reference genome). Some of them determine altered protein functions or the virus–host interaction and the related virus entry processes. The results obtained in this study constitute a first step towards the definition of a One Health strategy that includes cattle genetic resources as reservoirs of host gene variability useful to design conservation and selection programs to increase resistance to coronavirus diseases.

Zoonotic Origins of Human Metapneumovirus: A Journey from Birds to Humans.

Metapneumoviruses, members of the family Pneumoviridae, have been identified in birds (avian metapneumoviruses; AMPV’s) and humans (human metapneumoviruses; HMPV’s). AMPV and HMPV are closely related viruses with a similar genomic organization and cause respiratory tract illnesses in birds and humans, respectively. AMPV can be classified into four subgroups, A–D, and is the etiological agent of turkey rhinotracheitis and swollen head syndrome in chickens. Epidemiological studies have indicated that AMPV also circulates in wild bird species which may act as reservoir hosts for novel subtypes. HMPV was first discovered in 2001, but retrospective studies have shown that HMPV has been circulating in humans for at least 50 years. AMPV subgroup C is more closely related to HMPV than to any other AMPV subgroup, suggesting that HMPV has evolved from AMPV-C following zoonotic transfer. In this review, we present a historical perspective on the discovery of metapneumoviruses and discuss the host tropism, pathogenicity, and molecular characteristics of the different AMPV and HMPV subgroups to provide increased focus on the necessity to better understand the evolutionary pathways through which HMPV emerged as a seasonal endemic human respiratory virus.

Transcriptomics Reveal Several Novel Viruses from Canegrubs (Coleoptera: Scarabaeidae) in Central Queensland, Australia.

Canegrubs (Coleoptera: Scarabaeidae) are major pests of sugarcane crops in Australia, but despite long-term and intensive research, no commercially viable biological control agents have been identified. We used the RNA-Seq approach to explore the viriomes of three different species of canegrubs from central Queensland, Australia to identify potential candidates for biological control. We identified six novel RNA viruses, characterized their genomes, and inferred their evolutionary relationships with other closely related viruses. These novel viruses showed similarity to other known members from picornaviruses, benyviruses, sobemoviruses, totiviruses, and reoviruses. The abundance of viral reads varied in these libraries; for example, Dermolepida albohirtum picorna-like virus (9696 nt) was built from 83,894 assembled reads while only 1350 reads mapped to Lepidiota negatoria beny-like virus (6371 nt). Future studies are essential to determine their natural incidence in different life stages of the host, biodiversity, geographical distributions, and potential as biological control agents for these important pests of sugarcane.

Modeling Dengue Immune Responses Mediated by Antibodies: Insights on the Biological Parameters to Describe Dengue Infections

Dengue fever is a viral mosquito-borne disease, a significant global health concern, with more than one third of the world population at risk of acquiring the disease. Caused by 4 antigenically distinct but related virus serotypes, named DENV-1, DENV-2, DENV-3, and DENV-4, infection by one serotype confers lifelong immunity to that serotype and a short period of temporary cross immunity to other related serotypes. Severe dengue is epidemiologically associated with a secondary infection caused by a heterologous serotype via the so-called antibody-dependent enhancement (ADE), an immunological process enhancing a new infection. Within-host dengue modeling is restricted to a small number of studies so far. With many open questions, the understanding of immunopathogenesis of severe disease during recurrent infections is important to evaluate the impact of newly licensed vaccines. In this paper, we revisit the modeling framework proposed by Sebayang et al. and perform a detailed sensitivity analysis of the well-known biological parameters and its possible combinations to understand the existing data sets. Using numerical simulations, we investigate features of viral replication, antibody production, and infection clearance over time for three possible scenarios: primary infection, secondary infection caused by homologous serotype, and secondary infection caused by heterologous serotype. Besides, describing well the infection dynamics as reported in the immunology literature, our results provide information on parameter combinations to best describe the differences on the immunological dynamics of secondary infections with homologous and heterologous viruses. The results presented here will be used as baseline to investigate a more complex within-host dengue model.

SARS-CoV-2 gained a novel spike protein S1–N-Terminal Domain (S1-NTD)

The clue behind the SARS-CoV-2 origin is still a matter of debate. Here, we report that SARS-CoV-2 has gained a novel spike protein S1–N-terminal domain (S1-NTD). In our CLuster ANalysis of Sequences (CLANS) analysis, SARS-CoV/SARS-CoV-2 S1-NTDs displayed a close relationship with OC43 and HKU1. However, in the complete and S1-NTD-free spike protein, SARS-CoV/SARS-CoV-2 revealed closeness with MERS-CoV. Further, we have divided the S1-NTD of SARS-CoV-2 related viruses into three distinct types (Type-I to III S1-NTD) and the S1-NTD of viruses associated with SARS-CoVs into another three classes (Type-A to C S1-NTD) using CLANS and phylogenetic analyses. In particular, the results of our study indicate that SARS-CoV-2, RaTG13, and BANAL-20-52 viruses carry Type-I-S1-NTD and other SARS-CoV-2-related-bat viruses have Type-II and III. In addition, it was revealed that the Pangolin-GX and Pangolin-Guangdong lineages inherited Type-I-like and Type–II–like S1-NTD, respectively. Then our CLANS study shows the potential for evolution of Type-I and Type-III S1-NTD from SARS-CoV-related viruses Type-A and Type-B S1-NTDs, respectively. Furthermore, our analysis clarifies the possibility that Type-II S1-NTDs may have evolved from Type-A-S1-NTD of SARS-CoV-related viruses through Type-I S1-NTDs. We also observed that BANAL-20-103, BANAL-20-236, and Pangolin-Guangdong-lineage viruses containing Type–II–like S1-NTD are very close to SARS-CoV-2 in spike genetic areas other than S1-NTD. Possibly, it suggests that the common ancestor spike gene of SARS-CoV-2/RaTG13/BANAL-20-52-like virus may have evolved by recombining the Pangolin-Guangdong/BANAL-20-103/BANAL-20-236-like spike gene to Pangolin-GX-like Type-I-like-S1-NTD in the unsampled bat or undiscovered intermediate host or possibly pangolin. These may then have evolved into SARS-CoV-2, RaTG13, and BANAL-20-52 virus spike genes by host jump mediated evolution. The potential function of the novel Type-I-S1-NTD and other types of S1-NTDs needs to be studied further to understand better its importance in the ongoing COVID-19 outbreak and for future pandemic preparedness.

PWM2Vec: An Efficient Embedding Approach for Viral Host Specification from Coronavirus Spike Sequences.

Simple SummaryThe family of coronaviruses comprises a diverse set of strains and variants which cause diseases from the common cold to COVID-19. Moreover, they infect a wide array of hosts from bats, camels, birds, to humans. Studying coronaviruses through the lens of host specificity provides a unique perspective to understanding the evolution, diversity and dynamics of this family. In particular, this can reveal groups of different hosts infected by similar strains, giving clues on strains which were more likely to have evolved to jump from one host to another. In this work, we frame host specificity as a classification task, in designing a very compact numerical representation of the spike sequences of different coronaviruses. Based on this numerical representation, classification methods are able to detect the target host with high accuracy. Such an approach can used to efficiently scale to large volumes of sequences, in order to unveil trends in the host specificity of different coronavirus strains.The study of host specificity has important connections to the question about the origin of SARS-CoV-2 in humans which led to the COVID-19 pandemic—an important open question. There are speculations that bats are a possible origin. Likewise, there are many closely related (corona)viruses, such as SARS, which was found to be transmitted through civets. The study of the different hosts which can be potential carriers and transmitters of deadly viruses to humans is crucial to understanding, mitigating, and preventing current and future pandemics. In coronaviruses, the surface (S) protein, or spike protein, is important in determining host specificity, since it is the point of contact between the virus and the host cell membrane. In this paper, we classify the hosts of over five thousand coronaviruses from their spike protein sequences, segregating them into clusters of distinct hosts among birds, bats, camels, swine, humans, and weasels, to name a few. We propose a feature embedding based on the well-known position weight matrix (PWM), which we call PWM2Vec, and we use it to generate feature vectors from the spike protein sequences of these coronaviruses. While our embedding is inspired by the success of PWMs in biological applications, such as determining protein function and identifying transcription factor binding sites, we are the first (to the best of our knowledge) to use PWMs from viral sequences to generate fixed-length feature vector representations, and use them in the context of host classification. The results on real world data show that when using PWM2Vec, machine learning classifiers are able to perform comparably to the baseline models in terms of predictive performance and runtime—in some cases, the performance is better. We also measure the importance of different amino acids using information gain to show the amino acids which are important for predicting the host of a given coronavirus. Finally, we perform some statistical analyses on these results to show that our embedding is more compact than the embeddings of the baseline models.

Evidence of SARS-CoV-2 Related Coronaviruses Circulating in Sunda pangolins (Manis javanica) Confiscated From the Illegal Wildlife Trade in Viet Nam

Despite the discovery of several closely related viruses in bats, the direct evolutionary progenitor of SARS-CoV-2 has not yet been identified. In this study, we investigated potential animal sources of SARS-related coronaviruses using archived specimens from Sunda pangolins (Manis javanica) and Chinese pangolins (Manis pentadactyla) confiscated from the illegal wildlife trade, and from common palm civets (Paradoxurus hermaphroditus) raised on wildlife farms in Viet Nam. A total of 696 pangolin and civet specimens were screened for the presence of viral RNA from five zoonotic viral families and from Sarbecoviruses using primers specifically designed for pangolin coronaviruses. We also performed a curated data collection of media reports of wildlife confiscation events involving pangolins in Viet Nam between January 2016 and December 2020, to illustrate the global pangolin supply chain in the context of Viet Nam where the trade confiscated pangolins were sampled for this study. All specimens from pangolins and civets sampled along the wildlife supply chains between February 2017 and July 2018, in Viet Nam and tested with conventional PCR assays designed to detect flavivirus, paramyxovirus, filovirus, coronavirus, and orthomyxovirus RNA were negative. Civet samples were also negative for Sarbecoviruses, but 12 specimens from seven live pangolins confiscated in Hung Yen province, northern Viet Nam, in 2018 were positive for Sarbecoviruses. Our phylogenetic trees based on two fragments of the RdRp gene revealed that the Sarbecoviruses identified in these pangolins were closely related to pangolin coronaviruses detected in pangolins confiscated from the illegal wildlife trade in Yunnan and Guangxi provinces, China. Our curated data collection of media reports of wildlife confiscation events involving pangolins in Viet Nam between January 2016 and December 2020, reflected what is known about pangolin trafficking globally. Pangolins confiscated in Viet Nam were largely in transit, moving toward downstream consumers in China. Confiscations included pangolin scales sourced originally from Africa (and African species of pangolins), or pangolin carcasses and live pangolins native to Southeast Asia (predominately the Sunda pangolin) sourced from neighboring range countries and moving through Viet Nam toward provinces bordering China.