Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition ...system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.
Abstract
Wild mammalian species, including bats, constitute the natural reservoir of betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2). Different hosts or host tissues provide ...different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence. Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. The author shows that SARS-CoV-2 has the most extreme CpG deficiency in all known betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression. A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (alphacoronavirus) as possessing the most extreme CpG deficiency, comparable with that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.
Abstract The rapid spread and remarkable mutations of SARS‐CoV‐2 variants, particularly Omicron, necessitate an understanding of their evolutionary characteristics. In this study, we analyzed ...representative high‐quality whole‐genome sequences of 2008 SARS‐CoV‐2 variants to explore long‐term dynamic changes in genomic base (especially GC) content and variations during viral evolution. Our results demonstrated a highly negative correlation between GC content and variant emergence time ( r = −0.765, p < 2.22e−16). Major gene partitions (S, N, ORF1ab) displayed similar trends. Omicron exhibited a significantly lower GC content than non‐Omicron variants ( p < 2.22e−16). Notably, we observed a robust negative correlation between C and T content ( r = −0.778, p < 2.22e−16) and between G and A content ( r = −0.773, p < 2.22e−16). Among all strains, Omicron showed the greatest base variation, with C‐>T mutations being the most frequent (median interquartile range IQR: 29 (27, 31), 37.67%), succeeded by G‐>A mutations (11 (9, 13), 14.63%). Over a 3‐year span, an annual decline rate of 0.12% in SARS‐CoV‐2 GC content was observed and could become more pronounced in future emerging variants. These findings provided insights into the evolutionary trajectory of SARS‐CoV‐2, underscoring the significance of continuous genomic surveillance for effective prediction of and response to future variants.
To study virus-host protein interactions, knowledge about viral and host protein architectures and repertoires, their particular evolutionary mechanisms, and information on relevant sources of ...biological data is essential. The purpose of this review article is to provide a thorough overview about these aspects. Protein domains are basic units defining protein interactions, and the uniqueness of viral domain repertoires, their mode of evolution, and their roles during viral infection make viruses interesting models of study. Mutations at protein interfaces can reduce or increase their binding affinities by changing protein electrostatics and structural properties. During the course of a viral infection, both pathogen and cellular proteins are constantly competing for binding partners. Endogenous interfaces mediating intraspecific interactions-viral-viral or host-host interactions-are constantly targeted and inhibited by exogenous interfaces mediating viral-host interactions. From a biomedical perspective, blocking such interactions is the main mechanism underlying antiviral therapies. Some proteins are able to bind multiple partners, and their modes of interaction define how fast these "hub proteins" evolve. "Party hubs" have multiple interfaces; they establish simultaneous/stable (domain-domain) interactions, and tend to evolve slowly. On the other hand, "date hubs" have few interfaces; they establish transient/weak (domain-motif) interactions by means of short linear peptides (15 or fewer residues), and can evolve faster. Viral infections are mediated by several protein-protein interactions (PPIs), which can be represented as networks (protein interaction networks, PINs), with proteins being depicted as nodes, and their interactions as edges. It has been suggested that viral proteins tend to establish interactions with more central and highly connected host proteins. In an evolutionary arms race, viral and host proteins are constantly changing their interface residues, either to evade or to optimize their binding capabilities. Apart from gaining and losing interactions via rewiring mechanisms, virus-host PINs also evolve via gene duplication (paralogy); conservation (orthology); horizontal gene transfer (HGT) (xenology); and molecular mimicry (convergence). The last sections of this review focus on PPI experimental approaches and their limitations, and provide an overview of sources of biomolecular data for studying virus-host protein interactions.
The intestinal microbiota and human health are intimately linked, but interactions between bacteria and bacteriophages in the context of the mammalian intestine remain largely unexplored. We used ...comparative population genomics to study a tripartite network consisting of a virulent bacteriophage, its bacterial host, and a phage-insensitive bacterial strain both in vitro and within the murine gut. The bacteriophage adapted to infect the insensitive strain when the three partners co-existed in the gut of conventional mice, but not in dixenic mice or in planktonic cultures. The molecular changes associated with modifications in the bacteriophage host spectrum included single amino acid substitutions and an unusual homologous intragenomic recombination event within the genome of the bacteriophage. An intermediate bacterial host isolated from the murine microbiota mediated bacteriophage adaptation. Our data indicate that by offering access to new hosts, the microbiota shifts the genetic diversity of bacteriophages, thereby promoting long-term persistence of bacteriophage populations.
Display omitted
•Bacteriophage host jumps occur in the gut of mice but not in vitro•Intermediate hosts from the microbiota promote modification of bacteriophage host range•Homologous intragenomic recombination events are associated with host jump•A single point mutation in a tail fiber gene is sufficient for a host jump
The mechanisms underlying the dynamic co-evolution of bacteriophages and bacteria within the gut microbiota remain unclear. By coupling in vitro and animal experiments, De Sordi et al. show that the diverse bacterial community within the gut is an evolutionary force that promotes diversification of bacteriophage infectivity including host jumps.
The SARS-CoV-2 Hydra with many heads (variants) has been causing the COVID-19 pandemic for 3 years. The appearance of every new head (SARS-CoV-2 variant) causes a new pandemic wave. The last in the ...series is the XBB.1.5 “Kraken” variant. In the general public (social media) and in the scientific community (scientific journals), during the last several weeks since the variant has appeared, the question was raised of whether the infectivity of the new variant will be greater. This article attempts to provide the answer. Analysis of thermodynamic driving forces of binding and biosynthesis leads to the conclusion that infectivity of the XBB.1.5 variant could be increased to a certain extent. The pathogenicity of the XBB.1.5 variant seems to be unchanged compared to the other Omicron variants.
Giant viruses are remarkable for their large genomes, often rivaling those of small bacteria, and for having genes thought exclusive to cellular life. Most isolated to date infect nonmarine protists, ...leaving their strategies and prevalence in marine environments largely unknown. Using eukaryotic single-cell metagenomics in the Pacific, we discovered a Mimiviridae lineage of giant viruses, which infects choanoflagellates, widespread protistan predators related to metazoans. The ChoanoVirus genomes are the largest yet from pelagic ecosystems, with 442 of 862 predicted proteins lacking known homologs. They are enriched in enzymes formodifying organic compounds, including degradation of chitin, an abundant polysaccharide in oceans, and they encode 3 divergent type-1 rhodopsins (VirR) with distinct evolutionary histories from those that capture sunlight in cellular organisms. One (VirRDTS) is similar to the only other putative rhodopsin from a virus (PgV) with a known host (a marine alga). Unlike the algal virus, ChoanoViruses encode the entire pigment biosynthesis pathway and cleavage enzyme for producing the required chromophore, retinal. We demonstrate that the rhodopsin shared by ChoanoViruses and PgV binds retinal and pumps protons. Moreover, our 1.65-Å resolved VirRDTS crystal structure and mutational analyses exposed differences from previously characterized type-1 rhodopsins, all of which come from cellular organisms. Multiple VirR types are present in metagenomes from across surface oceans, where they are correlated with and nearly as abundant as a canonical marker gene from Mimiviridae . Our findings indicate that light-dependent energy transfer systems are likely common components of giant viruses of photosynthetic and phagotrophic unicellular marine eukaryotes.
Through antigenic evolution, viruses such as seasonal influenza evade recognition by neutralizing antibodies. This means that a person with antibodies well tuned to an initial infection will not be ...protected against the same virus years later and that vaccine-mediated protection will decay. To expand our understanding of which endemic human viruses evolve in this fashion, we assess adaptive evolution across the genome of 28 endemic viruses spanning a wide range of viral families and transmission modes. Surface proteins consistently show the highest rates of adaptation, and ten viruses in this panel are estimated to undergo antigenic evolution to selectively fix mutations that enable the escape of prior immunity. Thus, antibody evasion is not an uncommon evolutionary strategy among human viruses, and monitoring this evolution will inform future vaccine efforts. Additionally, by comparing overall amino acid substitution rates, we show that SARS-CoV-2 is accumulating protein-coding changes at substantially faster rates than endemic viruses.
Display omitted
•Ongoing adaptive evolution in human endemic viruses is largely in surface proteins•Immune evasion drives continuous adaptive evolution in many endemic human viruses•Antigenic evolution occurs in several viral families•SARS-CoV-2 is accumulating protein-coding changes faster than other endemic viruses
Kistler and Bedford examine the genomes of 28 human endemic viruses and estimate that 10 of these viruses are undergoing antigenic evolution. This demonstrates that evasion of antibody detection is not an uncommon evolutionary strategy among the viruses that commonly infect humans.
Porcine epidemic diarrhea virus (PEDV), which classified in the genus
Alphacoronavirus
, family
Coronaviridae
, is one of the most important pathogens that cause heavy economic losses in pig ...industry. Although intensive mutation and recombination analysis of PEDV strains were provided, systematic genome analysis were needed to elucidate the evolution mechanism and codon usage adaptation profiles of the pathogen. Here, a comprehensive investigation was carried out to reveal the systematic evolutionary processes of synonymous codon usage and host-adapted evolution phenotype of PEDV genome. We found a low codon usage bias (CUB) in PEDV genome and that nucleotide compositions, natural selection, mutation pressure and geographical diversity shapes the codon usage patterns of PEDV, with natural selection dominated the overall codon usage bias in PEDV than the others. By using the relative codon deoptimization index (RCDI) and similarity index (SiD) analysis, we observed that genotype II PEDV strains showed the highest level of adaptation phenotype to
Sus scrofa
than another divergent clade. To the best of our knowledge, this is the first comprehensive report elaborating the codon usage and host adaptation of PEDV. The findings offer an insight into our understanding of factors involved in PEDV evolution, adaptation and fitness toward their hosts.
Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over ...70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere.
PDF
