Coevolution Of Virus Research Articles

Discovery of the first sea turtle adenovirus and turtle associated circoviruses

Turtles are an evolutionarily unique and morphologically distinctive order of reptiles, and many species are globally endangered. Although a high diversity of adenoviruses in scaled reptiles is well-documented, turtle adenoviruses remain largely understudied. To investigate their molecular diversity, we focused on the identification and characterisation of adenoviruses in turtle-derived organ, swab and egg samples. Since reptile circoviruses have been scarcely reported and no turtle circoviruses have been documented to date, we also screened our samples for circoviruses. Host−virus coevolution is a common feature of these viral families, so we aimed to investigate possible signs of this as well. Two screening projects were conducted: one on Brazilian samples collected from animals in their natural habitat, and the other on Hungarian pet shop samples. Nested PCR systems were used for the detection of adeno- and circoviruses and purified PCR products were Sanger sequenced. Phylogenetic trees for the viruses were reconstructed based on the adenoviral DNA polymerase and hexon genes, circoviral Rep genes, and for the turtle hosts based on mitochondrial cytochrome b amino acid sequences. During the screening, testadeno-, siadeno-, and circovirus strains were detected. The circovirus strains were classified into the genus Circovirus, exhibiting significant evolutionary divergence but forming a monophyletic clade within a group of fish circoviruses. The phylogenetic tree of turtles reflected their taxonomic relationships, showing a deep bifurcation between suborders and distinct monophyletic clades corresponding to families. A similar clustering pattern was observed among the testadenovirus strains in their phylogenetic tree. As a result, this screening of turtle samples revealed at least three new testadenoviruses, including the first sea turtle adenovirus, evidence of coevolution between testadenoviruses and their hosts, and the first turtle associated circoviruses. These findings underscore the need for further research on viruses in turtles, and more broadly in reptiles, to better understand their viral diversity and the evolutionary processes shaping host–virus interactions.

Quasineutral multistability in an epidemiological-like model for defective-helper betacoronavirus infection in cell cultures

It is well known that, during replication, RNA viruses spontaneously generate defective viral genomes (DVGs). DVGs are unable to complete an infectious cycle autonomously and depend on coinfection with a wild-type helper virus (HV) for their replication and/or transmission. The study of the dynamics arising from a HV and its DVGs has been a longstanding question in virology. It has been shown that DVGs can modulate HV replication and, depending on the strength of interference, result in HV extinctions or self-sustained persistent fluctuations. Extensive experimental work has provided mechanistic explanations for DVG generation and compelling evidences of HV-DVGs virus coevolution. Some of these observations have been captured by mathematical models. Here, we develop and investigate an epidemiological-like mathematical model specifically designed to study the dynamics of betacoronavirus in cell culture experiments. The dynamics of the model is governed by several degenerate normally hyperbolic invariant manifolds given by quasineutral planes - i.e., filled by equilibrium points. Three different quasineutral planes have been identified depending on parameters and involving: (i) persistence of HV and DVGs; (ii) persistence of non-infected cells and DVG-infected cells; and (iii) persistence of DVG-infected cells and DVGs. Key parameters involved in these scenarios are the maximum burst size (B), the fraction of DVGs produced during HV replication (β), and the replication advantage of DVGs (δ). More precisely, in the case 0<B<1+β the system displays tristability, where all three scenarios are present. In the case 1+β<B<1+β+δ this tristability persists but attracting scenario (ii) is reduced to a well-defined half-plane. For B>1+β+δ, the scenario (i) becomes globally attractor. Scenarios (ii) and (iii) are compatible with the so-called self-curing since the HV is removed from the population. Sensitivity analyses indicate that model dynamics largely depend on DVGs production rate (β) and their replicative advantage (δ), and on both the infection rates and virus-induced cell deaths. Finally, the model has been fitted to single-passage experimental data using an artificial intelligence methodology based on genetic algorithms and key virological parameters have been estimated.

Complete genome characterization and phylogenetic analysis of a novel polyomavirus detected in Eurasian beavers (Castor fiber)

The Eurasian beaver (Castor fiber), native to Hungary, faced local extinction in 1865 and was successfully reintroduced between mid-1980s and 2008. Despite screening programs focusing on animal health during reintroduction in other countries, information about viruses in the Hungarian beaver population remains limited. Polyomaviruses (PyVs) have been identified in various rodents, and have been detected just recently in beavers by us. In this paper we present the full genome analysis of the first PyV detected in Eurasian beaver. The novel PyV was discovered in the kidney tissues of two specimens. The genome is 5244 bp, and contains four genes. Small T-antigen (STAg) and alternative large T ORF (ALTO) genes are directly fused together forming the middle T-antigen (MTAg). VP3 is absent from the genome. Its large T-antigen (LTAg) coding sequence exhibited over 15% genetic divergence from known PyVs, supporting its classification into a new species within the genus Alphapolyomavirus, suggesting to be named Alphapolyomavirus castoris. Phylogenetic analysis, based on the LTAg gene showed, that the beaver PyV forms a distinct clade with primate PyVs within the genus Alphapolyomavirus, separate from other rodent PyVs. Phylogenetic study of the VP1 gene however showed this virus to belong in a distinct clade with the same primate PyVs, and additionally PyVs from rodents and a myocastor, which suggest host virus co-evolution. The virus detection of the euthanized beavers suggests an apathogenic persistent infections. The aquatic lifestyle of beavers may influence virus transmission, warranting further exploration of undiscovered viruses in beavers.

The Role of Noncoding RNA in the Transmission and Pathogenicity of Flaviviruses.

Noncoding RNAs (ncRNAs) constitute a class of RNA molecules that lack protein-coding capacity. ncRNAs frequently modulate gene expression through specific interactions with target proteins or messenger RNAs, thereby playing integral roles in a wide array of cellular processes. The Flavivirus genus comprises several significant members, such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV), which have caused global outbreaks, resulting in high morbidity and mortality in human populations. The life cycle of arthropod-borne flaviviruses encompasses their transmission between hematophagous insect vectors and mammalian hosts. During this process, a complex three-way interplay occurs among the pathogen, vector, and host, with ncRNAs exerting a critical regulatory influence. ncRNAs not only constitute a crucial regulatory mechanism that has emerged from the coevolution of viruses and their hosts but also hold potential as antiviral targets for controlling flavivirus epidemics. This review introduces the biogenesis of flavivirus-derived ncRNAs and summarizes the regulatory roles of ncRNAs in viral replication, vector-mediated viral transmission, antiviral innate immunity, and viral pathogenicity. A profound comprehension of the interplay between ncRNAs and flaviviruses will help formulate efficacious prophylactic and therapeutic strategies against flavivirus-related diseases.

Parallel evolution and enhanced virulence upon in vivo passage of an RNA virus in Drosophila melanogaster.

Virus evolution is strongly affected by antagonistic co-evolution of virus and host. Host immunity positively selects for viruses that evade the immune response, which in turn may drive counter-adaptations in host immune genes. We investigated how host immune pressure shapes virus populations, using the fruit fly Drosophila melanogaster and its natural pathogen Drosophila C virus (DCV), as a model. We performed an experimental evolution study in which DCV was serially passaged for ten generations in three fly genotypes differing in their antiviral RNAi response: wild-type flies and flies in which the endonuclease gene Dicer-2 was either overexpressed or inactivated. All evolved virus populations replicated more efficiently in vivo and were more virulent than the parental stock. The number of polymorphisms increased in all three host genotypes with passage number, which was most pronounced in Dicer-2 knockout flies. Mutational analysis showed strong parallel evolution, as mutations accumulated in a specific region of the VP3 capsid protein in every lineage in a host genotype-independent manner. The parental tyrosine at position ninety-five of VP3 was substituted with either one of five different amino acids in fourteen out of fifteen lineages. However, no consistent amino acid changes were observed in the viral RNAi suppressor gene 1A, nor elsewhere in the genome in any of the host backgrounds. Our study indicates that the RNAi response restricts the sequence space that can be explored by viral populations. Moreover, our study illustrates how evolution towards higher virulence can be a highly reproducible, yet unpredictable process.

Repeated loss of the ability of a wild pepper disease resistance gene to function at high temperatures suggests that thermoresistance is a costly trait.

Specificity in plant-pathogen gene-for-gene (GFG) interactions is determined by the recognition of pathogen proteins by the products of plant resistance (R) genes. The evolutionary dynamics of R genes in plant-virus systems is poorly understood. We analyse the evolution of the L resistance locus to tobamoviruses in the wild pepper Capsicum annuum var. glabriusculum (chiltepin), a crop relative undergoing incipient domestication. The frequency, and the genetic and phenotypic diversity, of the L locus was analysed in 41 chiltepin populations under different levels of human management over its distribution range in Mexico. The frequency of resistance was lower in Cultivated than in Wild populations. L-locus genetic diversity showed a strong spatial structure with no isolation-by-distance pattern, suggesting environment-specific selection, possibly associated with infection by the highly virulent tobamoviruses found in the surveyed regions. L alleles differed in recognition specificity and in the expression of resistance at different temperatures, broad-spectrum recognition of P0 + P1 pathotypes and expression above 32°C being ancestral traits that were repeatedly lost along L-locus evolution. Overall, loss of resistance co-occurs with incipient domestication and broad-spectrum resistance expressed at high temperatures has apparent fitness costs. These findings contribute to understand the role of fitness trade-offs in plant-virus coevolution.

Evolutionary stability of antigenically escaping viruses.

Antigenic variation is the main immune escape mechanism for RNA viruses like influenza or SARS-CoV-2. While high mutation rates promote antigenic escape, they also induce large mutational loads and reduced fitness. It remains unclear how this cost-benefit trade-off selects the mutation rate of viruses. Using a traveling wave model for the coevolution of viruses and host immune systems in a finite population, we investigate how immunity affects the evolution of the mutation rate and other nonantigenic traits, such as virulence. We first show that the nature of the wave depends on how cross-reactive immune systems are, reconciling previous approaches. The immune-virus system behaves like a Fisher wave at low cross-reactivities, and like a fitness wave at high cross-reactivities. These regimes predict different outcomes for the evolution of nonantigenic traits. At low cross-reactivities, the evolutionarily stable strategy is to maximize the speed of the wave, implying a higher mutation rate and increased virulence. At large cross-reactivities, where our estimates place H3N2 influenza, the stable strategy is to increase the basic reproductive number, keeping the mutation rate to a minimum and virulence low.

The Past Is Present: Co-Evolution of Viruses and Host Resistance Within Geographic Centers of Plant Diversity.

Understanding the coevolutionary history of plants, pathogens, and disease resistance is vital for plant pathology. Here, I review Francis O. Holmes's work with tobacco mosaic virus (TMV) framed by the foundational work of Nikolai Vavilov on the geographic centers of origin of plants and crop wild relatives (CWRs) and T. Harper Goodspeed's taxonomy of the genus Nicotiana. Holmes developed a hypothesis that the origin of host resistance to viruses was due to coevolution of both at a geographic center. In the 1950s, Holmes proved that genetic resistance to TMV, especially dominant R-genes, was centered in South America for Nicotiana and other solanaceous plants, including Capsicum, potato, and tomato. One seeming exception was eggplant (Solanum melongena). Not until the acceptance of plate tectonics in the 1960s and recent advances in evolutionary taxonomy did it become evident that northeast Africa was the home of eggplant CWRs, far from Holmes's geographic center for TMV-R-gene coevolution. Unbeknownst to most plant pathologists, Holmes's ideas predated those of H.H. Flor, including experimental proof of the gene-for-gene interaction, identification of R-genes, and deployment of dominant host genes to protect crop plants from virus-associated yield losses. Expected final online publication date for the Annual Review of Phytopathology, Volume 61 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Plant virus movement proteins originated from jelly-roll capsid proteins.

Numerous, diverse plant viruses encode movement proteins (MPs) that aid the virus movement through plasmodesmata, the plant intercellular channels. MPs are essential for virus spread and propagation in distal tissues, and several unrelated MPs have been identified. The 30K superfamily of MPs (named after the molecular mass of tobacco mosaic virus (TMV) MP, the classical model of plant virology) is the largest and most diverse MP variety, represented in 16 virus families, but its evolutionary origin remained obscure. Here, we show that the core structural domain of the 30K MPs is homologous to the jelly-roll domain of the capsid proteins (CPs) of small RNA and DNA viruses, in particular, those infecting plants. The closest similarity was observed between the 30K MPs and the CPs of the viruses in the families Bromoviridae and Geminiviridae. We hypothesize that the MPs evolved via duplication or horizontal acquisition of the CP gene in a virus that infected an ancestor of vascular plants, followed by neofunctionalization of one of the paralogous CPs, potentially through the acquisition of unique N- and C-terminal regions. During the subsequent coevolution of viruses with diversifying vascular plants, the 30K MP genes underwent explosive horizontal spread among emergent RNA and DNA viruses, likely permitting viruses of insects and fungi that coinfected plants to expand their host ranges, molding the contemporary plant virome.

Evasion strategies of porcine reproductive and respiratory syndrome virus.

During the co-evolution of viruses and their hosts, viruses have developed various strategies for overcoming host immunological defenses so that they can proliferate efficiently. Porcine reproductive and respiratory syndrome virus (PRRSV), a significant virus to the swine industry across the world, typically establishes prolonged infection via diverse and complicated mechanisms, which is one of the biggest obstacles for controlling the associated disease, porcine reproductive and respiratory syndrome (PRRS). In this review, we summarize the latest research on how PRRSV circumvents host antiviral responses from both the innate and adaptive immune systems and how this virus utilizes other evasion mechanisms, such as the manipulation of host apoptosis and microRNA. A thorough understanding of the exact mechanisms of PRRSV immune evasion will help with the development of novel antiviral strategies against PRRSV.

Large-scale identification of known and novel RRNPP quorum sensing systems by RRNPP_detector captures novel features of bacterial, plasmidic and viral co-evolution.

Gram-positive Firmicutes bacteria and their mobile genetic elements (plasmids, bacteriophages) encode peptide-based quorum sensing systems (QSSs) that orchestrate behavioral transitions as a function of population densities. In their simplest form, termed "RRNPP", these QSSs are composed of two adjacent genes: a communication propeptide and its cognate intracellular receptor. RRNPP QSSs notably regulate social/competitive behaviors such as virulence or biofilm formation in bacteria, conjugation in plasmids or lysogeny in temperate bacteriophages. However, the genetic diversity and the prevalence of these communication systems, together with the breadth of behaviors they control, remain largely under-appreciated. To better assess the impact of density-dependency on microbial community dynamics and evolution, we developed the RRNPP_detector software, which predicts known and novel RRNPP QSSs in chromosomes, plasmids and bacteriophages of Firmicutes. Applying RRNPP_detector against available complete genomes of viruses and Firmicutes, we identified a rich repertoire of RRNPP QSSs from 11 already-known subfamilies and 21 novel high-confidence candidate subfamilies distributed across a vast diversity of taxa. The analysis of high-confidence RRNPP subfamilies notably revealed 14 subfamilies shared between chromosomes/plasmids/phages, 181 plasmids and 82 phages encoding multiple communication systems, phage-encoded QSSs predicted to dynamically modulate bacterial behaviors, and 196 candidate biosynthetic gene clusters under density-dependent regulation. Overall, our work enhances the field of quorum sensing research and reveals novel insights into the co-evolution of gram-positive bacteria and their mobile genetic elements.

Biogeochemical sulfur cycling of virus auxiliary metabolic genes involved in Napahai plateau wetland.

Virus plays important roles in regulating microbial community structure, horizontal gene transfer, and promoting biological evolution, also augmenting host metabolism during infection via the expression of auxiliary metabolic genes (AMGs), and thus affect biogeochemical cycling in the oceans. As the "kidney of the earth," wetlands have rich biodiversity and abundant resources. Based on metagenomic data, 10 AMGs associated with sulfur cycling, i.e., tusA, moaD, dsrE, soxA, soxB, soxC, soxD, soxX, soxY,and soxZ, were analyzed in Napahai plateau wetland. The phylogenetic trees of AMGs involved in sulfur metabolism from different habitats and host origins were constructed. Combined with principal coordinate analysis, it revealed that most AMGs associated with sulfur metabolism clustered separately, indicating the abundance and uniqueness in this region. The sulfur metabolism pathways involved by AMGs were mainly SOX systems, among which sulfur oxidation was associated with moaD and dsrE genes, while sulfur transport was related to tusA genes. It provides an insight into the biogeochemical sulfur cycling in plateau wetlands and lays the foundation for further study on the co-evolution of virus and host.

Cucumber Mosaic Virus-Induced Systemic Necrosis in Arabidopsis thaliana: Determinants and Role in Plant Defense.

Effector-triggered immunity (ETI) is one of the most studied mechanisms of plant resistance to viruses. During ETI, viral proteins are recognized by specific plant R proteins, which most often trigger a hypersensitive response (HR) involving programmed cell death (PCD) and a restriction of infection in the initially infected sites. However, in some plant-virus interactions, ETI leads to a response in which PCD and virus multiplication are not restricted to the entry sites and spread throughout the plant, leading to systemic necrosis. The host and virus genetic determinants, and the consequences of this response in plant-virus coevolution, are still poorly understood. Here, we identified an allelic version of RCY1-an R protein-as the host genetic determinant of broad-spectrum systemic necrosis induced by cucumber mosaic virus (CMV) infection in the Arabidopsis thaliana Co-1 ecotype. Systemic necrosis reduced virus fitness by shortening the infectious period and limiting virus multiplication; thus, this phenotype could be adaptive for the plant population as a defense against CMV. However, the low frequency (less than 1%) of this phenotype in A. thaliana wild populations argues against this hypothesis. These results expand current knowledge on the resistance mechanisms to virus infections associated with ETI in plants.

An extensive analysis of Codon usage pattern, Evolutionary rate, and Phylogeographic reconstruction in Foot and mouth disease (FMD) serotypes (A, Asia 1, and O) of six major climatic zones of India: A comparative study

Foot and mouth disease (FMD) is a major economically important viral disease of cloven-hoofed livestock globally. The FMD virus (FMDV) spreads widely in confined, cool, and humid climatic conditions. Being an RNA virus, FMDV is genetically unstable, and its genome evolution is highly influenced by mutational pressure. The climatic and environmental conditions have a significant impact on mutational pressure. The present study is a primary effort to establish a comprehensive relationship between climatic factors and the molecular evolutionary pattern of serotypes FMDV circulating in India. In this study, isolates of three serotypes (A, Asia 1, and O) were selected from six major climatic zones of India (Montane, Humid subtropical, Tropical wet and dry, Tropical wet, Semi-arid and Arid). Based on the full genome nucleotide sequence data, the codon usage bias, evolutionary and phylogeographic analysis was carried out. The study revealed that the codon use bias indicators in the FMDV serotypes differed significantly depending on the climatic zones. It implies that the selection and mutational pressure influence the codon usage pattern indices, with mutational pressure taking precedence in determining the codon usage bias of the FMDV genome. The tMRCA was estimated to be 1977, 1956, and 1953 for Indian FMD virus serotype-A, Asia 1, and O respectively which is around 32, 60, and 61 years before its actual identification in the field. Based on the evolutionary rates the serotype O is evolving rapidly compare to other serotypes in India. Virus transmission across the region was evident from the phylogeographic analysis. The integrated analysis of codon usage bias, evolutionary rate, and phylogeography analysis signifies the major role of mutational and selection pressure, implying that the FMD virus co-evolution and adaptations are highly influenced by climatic/environmental factors.

Single-Cell Sequencing Yields Insights in the Evolution of Foot-and-Mouth Disease Virus Persistent Infection.

Foot-and-mouth disease virus (FMDV) could cause acute infection in host cells, or they could coexist with host cells to generate persistent infection. In persistent infection, the virus could survive for a long time in the host and could be transmitted between different host cells. In the case of FMDV-persistent infection cell line, there is a remarkable significant cellular heterogeneity in the FMDV-persistent infection cell line due to differences of viral load in the individual cells within the cell line. However, the mechanisms of FMDV-persistent infection are not well understood. It is now generally accepted that multiple factors contribute to the coevolution of viruses and cells during the course of persistent infection. The outcome would influence the development of persistent FMDV infection conjointly, reaching a state of equilibrium ultimately. Therefore, in order to elucidate the mechanism of cellular heterogeneity in FMDV-persistent infection cell line, single-cell sequencing was performed on BHK-Op, and pseudotime trajectory plot was draw through cell cluster. Based on the cell clusters, we predicted the development and progression of the FMDV-persistent infection. It could be well explained by the fact that, in BHK-Op cells, there are a fraction of infected cells and a fraction of virus-exposed but uninfected bystander cells. By further comparing the transcripts in cell clusters, we found that these genes were involved in changes in ribosome biogenesis, cell cycle, and intracellular signaling including the interferon signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Through comprehensive cross-tabulation analysis of differential expressed genes in various cluster of cells, we identified a high association of Fos, a downstream transcription factor of the MAPK/extracellular signal–regulated kinase (ERK) signaling pathway, with viral replication during the formation of FMDV-persistent infection. Through the further study of Fos, we found that downregulation of Fos facilitates viral clearance during FMDV-persistent infection. Upregulation of c-Raf, which is the upstream of the MAPK/ERK signaling pathway, could promote FMDV replication through downregulation of Fos. Our research is the first to provide insight into the mechanism of the formation FMDV-persistent infection through single-cell sequencing using persistent infection cell line. Pseudotime trajectory analysis was the first time to apply for FMDV-persistent infection cell line. Our work highlights the detailed overview of the evolution of FMDV-persistent infection. We also analyzed the differential expressed genes in the replication or elimination of FMDV within the host. We found that the MAPK/ERK signaling pathway and its downstream transcription factor Fos play an important role in FMDV-persistent infection.

Genome of the parasitoid wasp Dinocampus coccinellae reveals extensive duplications, accelerated evolution, and independent origins of thelytokous parthenogeny and solitary behavior.

Dinocampus coccinellae (Hymenoptera: Braconidae) is a generalist parasitoid wasp that parasitizes >50 species of predatory lady beetles (Coleoptera: Coccinellidae), with thelytokous parthenogeny as its primary mode of reproduction. Here, we present the first high-quality genome of D. coccinellae using a combination of short- and long-read sequencing technologies, followed by assembly and scaffolding of chromosomal segments using Chicago + HiC technologies. We also present a first-pass ab initio and a reference-based genome annotation and resolve timings of divergence and evolution of (1) solitary behavior vs eusociality, (2) arrhenotokous vs thelytokous parthenogenesis, and (3) rates of gene loss and gain among Hymenopteran lineages. Our study finds (1) at least 2 independent origins of eusociality and solitary behavior among Hymenoptera, (2) 2 independent origins of thelytokous parthenogenesis from ancestral arrhenotoky, and (3) accelerated rates of gene duplications, loss, and gain along the lineages leading to D. coccinellae. Our work both affirms the ancient divergence of Braconid wasps from ancestral Hymenopterans and accelerated rates of evolution in response to adaptations to novel hosts, including polyDNA viral coevolution.

Unravelling cucumber resistance to several viruses via genome-wide association studies highlighted resistance hotspots and new QTLs.

The mapping and introduction of sustainable resistance to viruses in crops is a major challenge in modern breeding, especially regarding vegetables. We hence assembled a panel of cucumber elite lines and landraces from different horticultural groups for testing with six virus species. We mapped 18 quantitative trait loci (QTL) with a multiloci genome wide association studies (GWAS), some of which have already been described in the literature. We detected two resistance hotspots, one on chromosome 5 for resistance to the cucumber mosaic virus (CMV), cucumber vein yellowing virus (CVYV), cucumber green mottle mosaic virus (CGMMV) and watermelon mosaic virus (WMV), colocalizing with the RDR1 gene, and another on chromosome 6 for resistance to the zucchini yellowing mosaic virus (ZYMV) and papaya ringspot virus (PRSV) close to the putative VPS4 gene location. We observed clear structuring of resistance among horticultural groups due to plant virus coevolution and modern breeding which have impacted linkage disequilibrium (LD) in resistance QTLs. The inclusion of genetic structure in GWAS models enhanced the GWAS accuracy in this study. The dissection of resistance hotspots by local LD and haplotype construction helped gain insight into the panel's resistance introduction history. ZYMV and CMV resistance were both introduced from different donors in the panel, resulting in multiple resistant haplotypes at same locus for ZYMV, and in multiple resistant QTLs for CMV.

Treating symptomatic infections and the co-evolution of virulence and drug resistance.

Antimicrobial therapeutic treatments are by definition applied after the onset of symptoms, which tend to correlate with infection severity. Using mathematical epidemiology models, I explore how this link affects the coevolutionary dynamics between the virulence of an infection, measured via host mortality rate, and its susceptibility to chemotherapy. I show that unless resistance pre-exists in the population, drug-resistant infections are initially more virulent than drug-sensitive ones. As the epidemic unfolds, virulence is more counter-selected in drug-sensitive than in drug-resistant infections. This difference decreases over time and, eventually, the exact shape of genetic trade-offs govern long-term evolutionary dynamics. Using adaptive dynamics, I show that two types of evolutionary stable strategies (ESS) may be reached in the context of this simple model and that, depending on the parameter values, an ESS may only be locally stable. In general, the more the treatment rate increases with virulence, the lower the ESS value. Overall, both on the short-term and long-term, having treatment rate depend on infection virulence tend to favour less virulent strains in drug-sensitive infections. These results highlight the importance of the feedbacks between epidemiology, public health policies and parasite evolution, and have implications for the monitoring of virulence evolution.

Regulation of RNA Interference Pathways in the Insect Vector Laodelphax striatellus by Viral Proteins of Rice Stripe Virus.

RNA interference (RNAi), especially the small interfering RNA (siRNA) and microRNA (miRNA) pathways, plays an important role in defending against viruses in plants and insects. However, how insect-transmitted phytoviruses regulate the RNAi-mediated antiviral response in vector insects has barely been uncovered. In this study, we explored the interaction between rice stripe virus (RSV) and the miRNA and siRNA pathways of the small brown planthopper, which is a vector insect. The transcript and protein levels of key genes in the two RNAi pathways did not change during the RSV infection process. When the expression of insect Ago1, Ago2, or Translin was silenced by the injection of double-stranded RNAs targeting these genes, viral replication was promoted with Ago2 silencing but inhibited with Translin silencing. Protein-protein binding assays showed that viral NS2 and RNA-dependent RNA polymerase interacted with insect Ago2 and Translin, respectively. When NS2 was knocked down, the transcript level of Ago2 increased and viral replication was inhibited. Therefore, viral NS2 behaved like an siRNA suppressor in vector insects. This protein-binding regulation of insect RNAi systems reflects a complicated and diverse coevolution of viruses with their vector insects.

Immunity, virus evolution, and effectiveness of SARS-CoV-2 vaccines.

Phylogenetic and pathogenesis studies of the severe acute respiratory syndrome-related coronaviruses (SARS-CoVs) strains have highlighted some specific mutations that could confer the RNA genome fitness advantages and immunological resistance for their rapid spread in the human population. The analyses of 30 kb RNA SARS-CoVs genome sequences, protein structures, and functions have provided us a perspective of how host-virus protein-protein complexes act to mediate virus infection. The open reading frame (ORF)1a and ORF1b translation yields 16 non-structural (nsp1-16) and 6 accessory proteins (p6, p7a, p8ab, p9b) with multiple functional domains. Viral proteins recruit over 300 host partners forming hetero-oligomeric complexes enabling the viral RNA synthesis, packing, and virion release. Many cellular host factors and the innate immune cells through pattern-recognition receptors and intracellular RNA sensor molecules act to inhibit virus entry and intracellular replication. However, non-structural ORF proteins hijack them and suppress interferon synthesis and its antiviral effects. Pro-inflammatory chemokines and cytokines storm leads to dysfunctional inflammation, lung injury, and several clinical symptoms in patients. During the global pandemic, COVID-19 patients were identified with non-synonymous substitution of G614D in the spike protein, indicating virus co-evolution in host cells. We review findings that suggest that host RNA editing and DNA repair systems, while carrying on recombination, mutation, and repair of viral RNA intermediates, may facilitate virus evolution. Understanding how the host cell RNA replication process may be driven by SARS-CoV-2 RNA genome fitness will help the testing of vaccines effectiveness to multiple independent mutated coronavirus strains that will emerge.