Search Results (45)

Tomato spotted wilt virus (TSWV), belonging to the genus Orthotospovirus, is a significant pathogen through its infection of economically vital crops including tomato, tobacco, pepper, and other species worldwide. Given its substantial influence on the agricultural industry, in-depth research on TSWV is of great necessity. Several studies have been conducted on the dinucleotide preference of TSWV previously; however, the information regarding codon usage bias (CUB) and the virus’s adaptive evolution remains inconclusive. Here, a thorough analysis of TSWV was performed by utilizing five protein-coding sequences in order to investigate the characteristics of CUB. It has been observed that the TSWV protein-coding sequences are AU-rich, and codons ending with A or U are also preferred in these sequences. A consistently stable and preserved genomic composition characterized by a lower codon usage preference was also observed. Principal Component Analysis (PCA), neutrality analysis, and ENC-plot indicated that, in comparison to mutational pressure, natural selection has a more dominant influence on the CUB of TSWV. The codon adaptation index (CAI) demonstrated a more significant correlation between TSWV and Nicotiana tabacum. Meanwhile, the relative codon deoptimization index (RCDI) indicated a stronger correlation between TSWV and Solanum lycopersicum. This study is the first to systematically characterize the CUB of TSWV based on its protein-coding sequences, providing critical insights into viral genetic diversity, evolution mechanisms, and host adaptation. The findings advance understanding of plant-virus coevolution and inform virus-resistant crop breeding and antiviral strategies. Full article

The evolutionary arms race between host restriction factors and viral antagonists provides crucial insights into immune system evolution and viral adaptation. This study investigates the structural and evolutionary dynamics of the double-domain restriction factors A3F and A3G and their viral inhibitor, Vif, across diverse primate species. By constructing 3D structural homology models and integrating ancestral sequence reconstruction (ASR), we identified patterns of sequence diversity, structural conservation, and functional adaptation. Inactive CD1 (Catalytic Domain 1) domains displayed greater sequence diversity and more positive surface charges than active CD2 domains, aiding nucleotide chain binding and intersegmental transfer. Despite variability, the CD2 DNA-binding grooves remained structurally consistent with conserved residues maintaining critical functions. A3F and A3G diverged in loop 7’ interaction strategies, utilising distinct molecular interactions to facilitate their roles. Vif exhibited charge variation linked to host species, reflecting its coevolution with A3 proteins. These findings illuminate how structural adaptations and charge dynamics enable both restriction factors and their viral antagonists to adapt to selective pressures. Our results emphasize the importance of studying structural evolution in host–virus interactions, with implications for understanding immune defense mechanisms, zoonotic risks, and viral evolution. This work establishes a foundation for further exploration of restriction factor diversity and coevolution across species. Full article

Pseudorabies virus (PRV) establishes persistent latent infections by effectively evading the host’s antiviral innate immune response. PRV has developed sophisticated strategies to bypass immune surveillance through coevolution with its host. Currently, no effective vaccine exists to prevent or treat infections caused by emerging PRV variants, and the interactions between PRV and the host’s innate immune defenses remain incompletely understood. Nevertheless, ongoing research is uncovering insights that may lead to novel treatments and preventive approaches for herpesvirus-related diseases. This review summarizes recent advances in understanding how PRV disrupts key adaptors in immune signaling pathways to evade antiviral immunity. Additionally, we explored the intrinsic cellular defenses that play crucial roles in combating viral invasion. A deeper understanding of the immune evasion strategies of PRV could inform the development of new therapeutic targets and vaccines. Full article

The complement system is an evolutionarily ancient component of innate immunity that serves as an important first line of defense against pathogens, including viruses. In response to infection, the complement system can be activated by three distinct yet converging pathways (classical, lectin, and alternative) capable of engaging multiple antiviral host responses to confront acute, chronic, and recurrent viral infections. Complement can exert profound antiviral effects via multiple mechanisms including the induction of inflammation and chemotaxis to sites of infection, neutralization/opsonization of viruses and virally infected cells, and it can even shape adaptive immune responses. With millions of years of co-evolution and the ability to establish life-long infections, herpesviruses have evolved unique mechanisms to counter complement-mediated antiviral defenses, thus enabling their survival and replication within humans. This review aims to comprehensively summarize how human herpesviruses engage with the complement system and highlight our understanding of the role of complement in human cytomegalovirus (HCMV) infection, immunity, and viral replication. Herein we describe the novel and unorthodox roles of complement proteins beyond their roles in innate immunity and discuss gaps in knowledge and future directions of complement and HCMV research. Full article

Bats, with their virus tolerance, social behaviors, and mobility, are reservoirs for emerging viruses, including coronaviruses (CoVs) known for genetic flexibility. Studying the cophylogenetic link between bats and CoVs provides vital insights into transmission dynamics and host adaptation. Prior research has yielded valuable insights into phenomena such as host switching, cospeciation, and other dynamics concerning the interaction between CoVs and bats. Nonetheless, a distinct gap exists in the current literature concerning a comparative cophylogenetic analysis focused on elucidating the contributions of sequence fragments to the co-evolution between hosts and viruses. In this study, we analyzed the cophylogenetic patterns of 69 host–virus connections. Among the 69 host–virus links examined, 47 showed significant cophylogeny based on ParaFit and PACo analyses, affirming strong associations. Focusing on two proteins, ORF1ab and spike, we conducted a comparative analysis of host and CoV phylogenies. For ORF1ab, the specific window ranged in multiple sequence alignment (positions 520–680, 770–870, 2930–3070, and 4910–5080) exhibited the lowest Robinson–Foulds (RF) distance (i.e., 84.62%), emphasizing its higher contribution in the cophylogenetic association. Similarly, within the spike region, distinct window ranges (positions 0–140, 60–180, 100–410, 360–550, and 630–730) displayed the lowest RF distance at 88.46%. Our analysis identified six recombination regions within ORF1ab (positions 360–1390, 550–1610, 680–1680, 700–1710, 2060–3090, and 2130–3250), and four within the spike protein (positions 10–510, 50–560, 170–710, and 230–730). The convergence of minimal RF distance regions with combination regions robustly affirms the pivotal role of recombination in viral adaptation to host selection pressures. Furthermore, horizontal gene transfer reveals prominent instances of partial gene transfer events, occurring not only among variants within the same host species but also crossing host species boundaries. This suggests a more intricate pattern of genetic exchange. By employing a multifaceted approach, our comprehensive strategy offers a nuanced understanding of the intricate interactions that govern the co-evolutionary dynamics between bat hosts and CoVs. This deeper insight enhances our comprehension of viral evolution and adaptation mechanisms, shedding light on the broader dynamics that propel viral diversity. Full article

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. Full article

Viruses rely on host cells to replicate their genomes and assemble new viral particles. Thus, they have evolved intricate mechanisms to exploit host factors. Host cells, in turn, have developed strategies to inhibit viruses, resulting in a nuanced interplay of co-evolution between virus and host. This dynamic often involves competition for resources crucial for both host cell survival and virus replication. Iron and iron-containing cofactors, including iron–sulfur clusters, are known to be a heavily fought for resource during bacterial infections, where control over iron can tug the war in favor of the pathogen or the host. It is logical to assume that viruses also engage in this competition. Surprisingly, our knowledge about how viruses utilize iron (Fe) and iron–sulfur (FeS) clusters remains limited. The handful of reviews on this topic primarily emphasize the significance of iron in supporting the host immune response against viral infections. The aim of this review, however, is to organize our current understanding of how viral proteins utilize FeS clusters, to give perspectives on what questions to ask next and to propose important avenues for future investigations. Full article

Insect viruses have been described from numerous lineages, yet patterns of genetic exchange and viral prevalence, which are essential to understanding host–virus coevolution, are rarely studied. In Helicoverpa zea, the virus HzNV-2 can cause deformity of male and female genitalia, resulting in sterility. Using ddPCR, we found that male H. zea with malformed genitalia (agonadal) contained high levels of HzNV-2 DNA, confirming previous work. HzNV-2 was found to be prevalent throughout the United States, at more than twice the rate of the baculovirus HaSNPV, and that it contained several host-acquired DNA sequences. HzNV-2 possesses four recently endogenized lepidopteran genes and several more distantly related genes, including one gene with a bacteria-like sequence found in both host and virus. Among the recently acquired genes is cytosolic serine hydroxymethyltransferase (cSHMT). In nearly all tested H. zea, cSHMT contained a 200 bp transposable element (TE) that was not found in cSHMT of the sister species H. armigera. No other virus has been found with host cSHMT, and the study of this shared copy, including possible interactions, may yield new insights into the function of this gene with possible applications to insect biological control, and gene editing. Full article

A relevant aspect in the epidemiology of Tegumentary Leishmaniasis (TL) are the Leishmania parasites carrying a viral endosymbiont, Leishmania RNA Virus 1 (LRV1), a dsRNA virus. Leishmania parasites carrying LRV1 are prone to causing more severe TL symptoms, increasing the likelihood of unfavorable clinical outcomes. LRV1 has been observed in the cultured strains of five L. (Viannia) species, and host specificity was suggested when studying the LRV1 from L. braziliensis and L. guyanensis strains. The coevolution hypothesis of LRV1 and Leishmania was based on phylogenetic analyses, implying an association between LRV1 genotypes, Leishmania species, and their geographic origins. This study aimed to investigate LRV1 specificity relative to Leishmania (Viannia) species hosts by analyzing LRV1 from L. (Viannia) species. To this end, LRV1 was screened in L. (Viannia) species other than L. braziliensis or L. guyanensis, and it was detected in 11 out of 15 L. naiffi and two out of four L. shawi. Phylogenetic analyses based on partial LRV1 genomic sequencing supported the hypothesis of host specificity, as LRV1 clustered according to their respective Leishmania species’ hosts. These findings underscore the importance of investigating Leishmania and LRV1 coevolution and its impact on Leishmania (Viannia) species dispersion and pathogenesis in the American Continent. Full article

Mycoviruses are viruses that selectively infect and multiply in fungal cells. Malassezia is the most abundant fungus on human skin and is associated with a variety of conditions, including atopic eczema, atopic dermatitis, dandruff, folliculitis, pityriasis versicolor, and seborrheic dermatitis. Here, we conducted mycovirome studies on 194 public transcriptomes of Malassezia (2,568,212,042 paired-end reads) screened against all available viral proteins. Transcriptomic data were assembled de novo resulting in 1,170,715 contigs and 2,995,306 open reading frames (ORFs) that were subsequently tracked for potential viral sequences. Eighty-eight virus-associated ORFs were detected in 68 contigs from 28 Sequence Read Archive (SRA) samples. Seventy-five and thirteen ORFs were retrieved from transcriptomes of Malassezia globosa and Malassezia restricta, respectively. Phylogenetic reconstructions revealed three new mycoviruses belonging to the Totivirus genus and named Malassezia globosa-associated-totivirus 1 (MgaTV1); Malassezia restricta-associated-totivirus 1 (MraTV1) and Malassezia restricta-associated-totivirus 2 (MraTV2). These viral candidates extend our understanding of the diversity and taxonomy of mycoviruses as well as their co-evolution with their fungal hosts. These results reflected the unexpected diversity of mycoviruses hidden in public databases. In conclusion, this study sheds light on the discovery of novel mycoviruses and opens the door to study their impact on disease caused by the host fungus Malassezia and globally, their implication in clinical skin disorders. Full article

The phage T7 RNA polymerase (RNAP) and lysozyme form the basis of the widely used pET expression system for recombinant expression in the biotechnology field and as a tool in microbial synthetic biology. Attempts to transfer this genetic circuitry from Escherichia coli to non-model bacterial organisms with high potential have been restricted by the cytotoxicity of the T7 RNAP in the receiving hosts. We here explore the diversity of T7-like RNAPs mined directly from Pseudomonas phages for implementation in Pseudomonas species, thus relying on the co-evolution and natural adaptation of the system towards its host. By screening and characterizing different viral transcription machinery using a vector-based system in P. putida., we identified a set of four non-toxic phage RNAPs from phages phi15, PPPL-1, Pf-10, and 67PfluR64PP, showing a broad activity range and orthogonality to each other and the T7 RNAP. In addition, we confirmed the transcription start sites of their predicted promoters and improved the stringency of the phage RNAP expression systems by introducing and optimizing phage lysozymes for RNAP inhibition. This set of viral RNAPs expands the adaption of T7-inspired circuitry towards Pseudomonas species and highlights the potential of mining tailored genetic parts and tools from phages for their non-model host. Full article

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. Full article

Pathogens including viruses evolve in tandem with diversity in their animal and human hosts. For SARS-coV2, the focus is generally for understanding such coevolution on the virus spike protein, since it demonstrates high mutation rates compared to other genome regions, particularly in the receptor-binding domain (RBD). Viral sequences of the SARS-coV2 19B (S) clade and variants of concern from different continents were investigated, with a focus on the A.29 lineage, which presented with different mutational patterns within the 19B (S) lineages in order to learn more about how SARS-coV2 may have evolved and adapted to widely diverse populations globally. Results indicated that SARS-coV2 went through evolutionary constrains and intense selective pressure, particularly in Africa. This was manifested in a departure from neutrality with excess nonsynonymous mutations and a negative Tajima D consistent with rapid expansion and directional selection as well as deletion and deletion–frameshifts in the N-terminal domain (NTD region) of the spike protein. In conclusion, we hypothesize that viral transmission during epidemics through populations of diverse genomic structures and marked complexity may be a significant factor for the virus to acquire distinct patterns of mutations within these populations in order to ensure its survival and fitness, explaining the emergence of novel variants and strains. Full article

Over the millions of years-long co-evolution with their hosts, viruses have evolved plenty of mechanisms through which they are able to escape cellular anti-viral defenses and utilize cellular pathways and organelles for replication and production of infectious virions. In recent years, it has become clear that lipids play an important role during viral replication. Viruses use cellular lipids in a variety of ways throughout their life cycle. They not only physically interact with cellular membranes but also alter cellular lipid metabolic pathways and lipid composition to create an optimal replication environment. This review focuses on examples of how different viruses exploit cellular lipids in different cellular compartments during their life cycles. Full article

The human cytomegalovirus (CMV) immediate early 1 (IE1) protein has evolved as a multifunctional antagonist of intrinsic and innate immune mechanisms. In addition, this protein serves as a transactivator and potential genome maintenance protein. Recently, the crystal structures of the human and rat CMV IE1 (hIE1, rIE1) core domain were solved. Despite low sequence identity, the respective structures display a highly similar, all alpha-helical fold with distinct variations. To elucidate which activities of IE1 are either species-specific or conserved, this study aimed at a comparative analysis of hIE1 and rIE1 functions. To facilitate the quantitative evaluation of interactions between IE1 and cellular proteins, a sensitive NanoBRET assay was established. This confirmed the species-specific interaction of IE1 with the cellular restriction factor promyelocytic leukemia protein (PML) and with the DNA replication factor flap endonuclease 1 (FEN1). To characterize the respective binding surfaces, helix exchange mutants were generated by swapping hIE1 helices with the corresponding rIE1 helices. Interestingly, while all mutants were defective for PML binding, loss of FEN1 interaction was confined to the exchange of helices 1 and 2, suggesting that FEN1 binds to the stalk region of IE1. Furthermore, our data reveal that both hIE1 and rIE1 antagonize human STAT2; however, distinct regions of the respective viral proteins mediated the interaction. Finally, while PML, FEN1, and STAT2 binding were conserved between primate and rodent proteins, we detected that rIE1 lacks a chromatin tethering function suggesting that this activity is dispensable for rat CMV. In conclusion, our study revealed conserved and distinct functions of primate and rodent IE1 proteins, further supporting the concept that IE1 proteins underwent a narrow co-evolution with their respective hosts to maximize their efficacy in antagonizing innate immune mechanisms and supporting viral replication. Full article