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PubMed2024

Frequent nonhomologous replacement of replicative helicase loaders by viruses in Vibrionaceae.

Several microbial genomes lack textbook-defined essential genes. If an essential gene is absent from a genome, then an evolutionarily independent gene of unknown function complements its function. Here, we identified frequent nonhomologous replacement of an essential component of DNA replication initiation, a replicative helicase loader gene, in Vibrionaceae. Our analysis of Vibrionaceae genomes revealed two genes with unknown function, named vdhL1 and vdhL2, that were substantially enriched in genomes without the known helicase-loader genes. These genes showed no sequence similarities to genes with known function but encoded proteins structurally similar with a viral helicase loader. Analyses of genomic syntenies and coevolution with helicase genes suggested that vdhL1/2 encodes a helicase loader. The in vitro assay showed that Vibrio harveyi VdhL1 and Vibrio ezurae VdhL2 promote the helicase activity of DnaB. Furthermore, molecular phylogenetics suggested that vdhL1/2 were derived from phages and replaced an intrinsic helicase loader gene of Vibrionaceae over 20 times. This high replacement frequency implies the host's advantage in acquiring a viral helicase loader gene.

Vibrionaceae↗
PubMed2026

Tracing the evolution and diversity of human parvovirus B19 across human history.

Human parvovirus B19 (B19V) is an ubiquitously spread, exclusively human pathogen, mainly posing risks to children, as well as pregnant and immunocompromised individuals. Despite evidence of B19V infection of human populations as far back as 7,000 years, the evolutionary history of B19V remains poorly understood. In this study, we present B19V genomic data from the remains of 53 globally distributed individuals spanning more than 8,000 years, including 7 children. Our findings suggest that the most recent common ancestor of all present B19V lineages existed around 12,000 years ago, at the end of the last Ice Age. Additionally, we identified an extinct Eurasian clade that participated in the recombination event that led to the emergence of B19V genotype 2 (GT-2). We date this event to ∼3,200-1,800 BP, potentially in the greater Mediterranean area. Our study shows aspects of how ancient parvovirus variants arose, disseminated, and impacted human health through time.

ancient DNA↗
PubMed2025

Genome-scale evolution and phylodynamics of swine influenza A viruses in China: a genomic epidemiology study.

BACKGROUND: Pigs are recognised as crucial intermediate hosts for the emergence of influenza viruses of pandemic potential. As the largest pork-producing nation, China hosts a complex ecosystem of swine influenza viruses (SIVs). We aimed to investigate the evolutionary processes, spatiotemporal dynamics, and biological characteristics of SIVs in China. METHODS: From Jan 15, 2016, to Dec 22, 2020, we collected nasal swabs from pigs at eight abattoirs and 16 swine farms in the Guangdong, Henan, and Shandong provinces of China, as part of SIV surveillance. SIVs were detected with RT-PCR. Positive samples underwent viral isolation and genome sequencing. We analysed evolution and spatiotemporal dynamics using the whole genomes of isolated SIVs, as well as genome sequences of SIV isolates from human infections worldwide retrieved from the Global Initiative on Sharing All Influenza Data and GenBank Flu databases up to April 28, 2024. Viral sequences without a sample collection area or date were excluded from the analysis. Viral receptor-binding properties and in-vitro replication of strains isolated in this study were evaluated with a solid-phase binding assay and various cell lines, including Madin-Darby canine kidney cells, porcine alveolar macrophages, primary porcine trachea epithelial cells, human bronchial epithelioid, and human lung adenocarcinoma epithelial (A549) cells. Viral replication and transmission studies were conducted in 33 guinea pigs and 13 pigs. Additionally, we collected serum samples from pig farm workers and members of the general public recruited by the Third Affiliated Hospital of Sun Yat-sen University between Feb 28 and May 11, 2023, to detect specific antibodies against Eurasian avian-like A(H1) and human-like A(H3N2) SIVs using the haemagglutination inhibition assay. FINDINGS: 23 (1·3%) of 1818 nasal swabs collected in abattoirs had SIVs; 22 (0·9%) of 2375 swabs from swine farms had SIVs. Further viral isolation yielded 39 strains of SIV. We identified 534 A(H1N1), 69 A(H1N2), and 92 A(H3N2) SIVs, representing 20 genotypes within the Eurasian avian-like lineage, 14 within the classical swine A(H1) lineage, and 16 within the human-like A(H3N2) lineage. The introduction of the A(H1N1)pdm/09 virus significantly influenced the internal gene pool of SIVs, enhancing genotypic diversity in China. Notably, the Eurasian avian-like A(H1), classical swine A(H1), and human-like A(H3N2) lineages showed human-mediated spread over long distances between provinces, with the Eurasian avian-like A(H1) lineage showing the most prevalent spread pathways. Eurasian avian-like A(H1) SIVs showed a preference for binding to sialic acid α-2,6 glycan receptors, predominantly found in humans, resulting in an increased production of progeny viruses in human airway epithelial cells, as well as effective transmission and infectivity among guinea pigs and pigs. Among 54 eligible serum samples collected from pig farm workers (24 from slaughterhouses and 30 from swine farms), 23 (43%) were seropositive for Eurasian avian-like A(H1) SIVs and 46 (85%) for human-like A(H3N2) SIVs. Among 100 eligible samples from members of the general public, 14 (14%) were seropositive for Eurasian avian-like A(H1) SIVs and 85 (85%) for human-like A(H3N2) SIVs. INTERPRETATION: This study elucidates the evolutionary processes and spatiotemporal patterns of SIVs, highlighting potential risks to public health. These findings are crucial for informing public health interventions that aim to prevent future SIV epidemics in China and other countries worldwide. FUNDING: Scientific Innovation Strategy-Construction of High-Level Academy of Agriculture Science-Distinguished Scholar (R2020PY-JC001).

Animals↗
PubMed1979

Evolution of multiple genome mutations during long-term persistent infection by vesicular stomatitis virus.

Persistent infection of BHK21 cells was established with cloned vesicular somatitis virus plus purified Dl particles and maintained in vitro for over 5 years. After 1 year of persistence, the infectious virus RNA genome had evolved several oligonucleotide map changes, and numerous changes had accumulated by 3.5 years. Additional evolution occurred by the fourth year and continued until the fifth year. In contrast, repeated passage of virus in acute infections of several cell types in vitro or in vivo did not lead to detectable oligonucleotide map changes. The short Dl particle originally used to co-infect with infectious virus in establishing persistent infection has been displaced by an ever present and constantly changing population of other Dl particles of differing sizes and radically differing oligonucleotide maps. We conclude that the genomes of both infectious VSV and its Dl particles undergo continuous evolutionary change during years of persistence. In the infectious virus, these changes involve hundreds of mutations which are usually expressed as poorly replicating, temperature-sensitive, small plaque mutants. These are stable mutants which do not revert to wild-type when passaged repeatedly in acute infections at 37 or 33 degrees C. It appears that the sequestered intracellular environment of persistently infected cells favors rapid and continuous virus evolution.

Animals↗
PubMed2009

Directed evolution of adeno-associated virus for glioma cell transduction.

Glioblastoma multiforme (GBM) is a serious form of brain cancer for which there is currently no effective treatment. Alternative strategies such as adeno-associated virus (AAV) vector mediated-genetic modification of brain tumor cells with genes encoding anti-tumor proteins have shown promising results in preclinical models of GBM, although the transduction efficiency of these tumors is often low. As higher transduction efficiency of tumor cells should lead to enhanced therapeutic efficacy, a means to rapidly engineer AAV vectors with improved transduction efficiency for individual tumors is an attractive strategy. Here we tested the possibility of identifying high-efficiency AAV vectors for human U87 glioma cells by selection in culture of a newly constructed chimeric AAV capsid library generated by DNA shuffling of six different AAV cap genes (AAV1, AAV2, AAV5, AAVrh.8, AAV9, AAVrh.10). After seven rounds of selection, we obtained a chimeric AAV capsid that transduces U87 cells at high efficiency (97% at a dose of 10(4) genome copies/cell), and at low doses it was 1.45-1.6-fold better than AAV2, which proved to be the most efficient parental capsid. Interestingly, the new AAV capsid displayed robust gene delivery properties to all glioma cells tested (including primary glioma cells) with relative fluorescence indices ranging from 1- to 14-fold higher than AAV2. The selected vector should be useful for in vitro glioma research when efficient transduction of several cell lines is required, and provides proof-of-concept that an AAV library can be used to generate AAV vectors with enhanced transduction efficiency of glioma cells.

Capsid Proteins↗
PubMed2025

The potential impacts of human genetics on virus emergence.

Human monogenic traits can confer resistance to viral infection in exposed individuals or predisposition to severe disease in infected individuals. Enhanced susceptibility can be driven directly by mutations in genes essential for control of the virus or indirectly via the production of autoantibodies against components of host defense. While the impact of viruses on individuals carrying these genotypes permitted their identification and has been amply studied, little is known about the impact of these human genotypes on the natural history of viruses, including not only persisting but also emerging viruses. We envisage several scenarios, including the possibility that genetically susceptible individuals serve as patient zeros, superspreaders, or mutation incubators, or that genetically resistant individuals even permit the selection of new viral mutants. Viruses are continually shared between individuals and even host species, where they can benefit from adaption to new environments. Current human viruses, as well as novel viruses from animal reservoirs, will continue to threaten the human population. Improvements in the scale of human genomic sequencing and analysis will permit testing hypotheses about the impact of human genetics on the origin and trajectory of viral infections, including future pandemics, which may ultimately help to prevent or curtail impending outbreaks.

Humans↗
PubMedDate not supplied

[System e in acute hepatitis B].

HBeAg and Ab are investigated by simple radial immunodiffusion in dextrane following Magnius. 14 patients (28%) were HBeAg positive and 2 patients HBeAb positive (4%). HBsAg subtyping was ad in 6 cases and ay in further 5. No relation was found between both determinants and HBeAg. Six of the 10 patients with HBeAg in their sera developed chronic liver disease o fulminant hepatitis, while only 3 of the 21 HBeAg negative controls did so (p less than 0.05). HBeAg is a marker of the evolution of virus B hepatitis.

Antibodies, Viral↗
PubMed2025

Molecular Evolution and Zoonotic Potential of Muju Virus (Orthohantavirus puumalaense) in Craseomys regulus, Republic of Korea.

Orthohantavirus puumalaense causes hemorrhagic fever with renal syndrome in Europe, with Puumala virus (PUUV) as its primary representative. Muju virus (MUJV), harbored by Craseomys regulus, an Arvicolinae rodent species endemic to the Republic of Korea (ROK), is also a genotype of O. puumalaense. However, their genomic diversity and zoonotic potential remain largely unknown. To investigate their prevalence, 185 voles were collected from 23 regions of the ROK between 2012 and 2023. Serological assays detected anti-PUUV immunoglobulin G antibodies in five samples (3.1%), whereas reverse-transcription polymerase chain reaction confirmed MUJV RNA in identical specimens (2.7%). Amplicon-based nanopore sequencing facilitates near-complete genome recovery, enabling high-resolution comparative analysis. Phylogenetic analysis revealed distinct genetic lineages in Gangwon and Jeollabuk Provinces. Evolutionary rate estimates indicated greater sequence divergence in the S and L segments than in the M segment. A zoonotic risk assessment revealed that most MUJV variants exhibited moderate-to-high spillover potential. The molecular detection of MUJV in Cheorwon, Gangwon Province, expands its known geographic range and provides the first molecular evidence of MUJV circulation in this region. These findings highlight the need for continued surveillance and seroprevalence studies of MUJV to assess its potential for human exposure and public health relevance in the ROK.

Animals↗
PubMed2026

[Genomic evolution and epidemiological patterns of respiratory syncytial virus and their implications for surveillance and early warning].

Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants, young children and older adults. Based on global RSV genomic surveillance data, this review systematically summarizes the geographic distribution, seasonal epidemic patterns, and long-term evolutionary trends of RSV, with particular emphasis on the sustained circulation and evolutionary mechanisms of dominant genotypes such as ON1 in RSV-A and BA9 in RSV-B. Current evidence indicates that RSV transmission dynamics are tightly coupled with viral evolution. The G gene evolves relatively rapidly and contains multiple positively selected sites, suggesting an important role in immune escape and population adaptation. In recent years, changes in social behavior patterns and population immunity have further disrupted the seasonal rhythm of RSV and may have influenced the spread of dominant genotypes. Under routine respiratory infectious disease surveillance, strengthened genomic monitoring and integration of multi-source data are needed to improve early warning of abnormal RSV epidemics and variant-associated risks, thereby providing prospective evidence for protecting high-risk populations and informing public health decision-making.

Humans↗
PubMed2017

A directed evolution approach to select for novel Adeno-associated virus capsids on an HIV-1 producer T cell line.

A directed evolution approach was used to select for Adeno-associated virus (AAV) capsids that would exhibit more tropism toward an HIV-1 producer T cell line with the long-term goal of developing improved gene transfer vectors. A library of AAV variants was used to infect H9 T cells previously infected or uninfected by HIV-1 followed by AAV amplification with wild-type adenovirus. Six rounds of biological selection were performed, including negative selection and diversification after round three. The H9 T cells were successfully infected with all three wild-type viruses (AAV, adenovirus, and HIV-1). Four AAV cap mutants best representing the small number of variants emerging after six rounds of selection were chosen for further study. These mutant capsids were used to package an AAV vector and subsequently used to infect H9 cells that were previously infected or uninfected by HIV-1. A quantitative polymerase chain reaction assay was performed to measure cell-associated AAV genomes. Two of the four cap mutants showed a significant increase in the amount of cell-associated genomes as compared to wild-type AAV2. This study shows that directed evolution can be performed successfully to select for mutants with improved tropism for a T cell line in the presence of HIV-1.

Capsid↗
PubMed2025

Variable rates of SARS-CoV-2 evolution in chronic infections.

An important feature of the evolution of the SARS-CoV-2 virus has been the emergence of highly mutated novel variants, which are characterised by the gain of multiple mutations relative to viruses circulating in the general global population. Cases of chronic viral infection have been suggested as an explanation for this phenomenon, whereby an extended period of infection, with an increased rate of evolution, creates viruses with substantial genetic novelty. However, measuring a rate of evolution during chronic infection is made more difficult by the potential existence of compartmentalisation in the viral population, whereby the viruses in a host form distinct subpopulations. We here describe and apply a novel statistical method to study within-host virus evolution, identifying the minimum number of subpopulations required to explain sequence data observed from cases of chronic infection, and inferring rates for within-host viral evolution. Across nine cases of chronic SARS-CoV-2 infection in hospitalised patients we find that non-trivial population structure is relatively common, with five cases showing evidence of more than one viral population evolving independently within the host. The detection of non-trivial population structure was more common in severely immunocompromised individuals (p = 0.04, Fisher's Exact Test). We find cases of within-host evolution proceeding significantly faster, and significantly slower, than that of the global SARS-CoV-2 population, and of cases in which viral subpopulations in the same host have statistically distinguishable rates of evolution. Non-trivial population structure was associated with high rates of within-host evolution that were systematically underestimated by a more standard inference method.

Humans↗
PubMed2024

Gene transfer agents: The ambiguous role of selfless viruses in genetic exchange and bacterial evolution.

Gene transfer agents (GTAs) are genetic elements derived from ancestral bacteriophages that have become domesticated by the host. GTAs are present in diverse prokaryotic organisms, where they can facilitate horizontal gene transfer under certain conditions. Unlike typical bacteriophages, GTAs do not exhibit any preference for the replication or transfer of the genes encoding them; instead, they exhibit a remarkable capacity to package chromosomal, and sometimes extrachromosomal, DNA into virus-like capsids and disseminate it to neighboring cells. Because GTAs resemble defective prophages, identification of novel GTAs is not trivial. The detection of candidates relies on the genetic similarity to known GTAs, which has been fruitful in α-proteobacterial lineages but challenging in more distant bacteria. Here we consider several fundamental questions: What is the true prevalence of GTAs in prokaryote genomes? Given there are high costs for GTA production, what advantage do GTAs provide to the bacterial host to justify their maintenance? How is the bacterial chromosome recognized and processed for inclusion in GTA particles? This article highlights the challenges in comprehensively understanding GTAs' prevalence, function and DNA packaging method. Going forward, broad study of atypical GTAs and use of ecologically relevant conditions are required to uncover their true impact on bacterial chromosome evolution.

Gene Transfer, Horizontal↗
PubMedDate not supplied

The application of biotechnology to the control of foot-and-mouth disease virus.

Biotechnology, which less than 10 years ago was heralded as an alternative to epidemiology in providing the answers to the control of foot-and-mouth disease (FMD), has not fulfilled its initial promise. Instead it is now complementing epidemiology by providing extremely sensitive and specific tools for identifying and characterizing strains of FMD virus in diagnostic material. Considerable advances in our understanding of the evolution of the virus in different field situations has been made possible by the development and application of polymerase chain reaction and nucleotide sequencing techniques. The individual genes of FMD virus can now be cloned into a number of vectors and separately expressed and studied in isolation from the other viral proteins. Biotechnology has not provided a safe and effective vaccine to replace the conventional tissue culture derived vaccine that would have made FMD a disease of the past. FMD remains the most economically significant animal disease having a major influence on the international trade of animals and their products. The world distribution of FMD has remained almost unchanged over the last 20 years and a balance has been maintained between improved surveillance and diagnostic technology and the ever increasing legal and illegal international movement of animals and reduction in veterinary resources. Research continues on peptide, recombinant and vector expressed virus protein vaccines which could at any time yield a breakthrough, not only for FMD control but, using similar technology, for control of other viral diseases, human and animal. Until this occurs, control and eradication of FMD still relies on classical epidemiological techniques, making use of new biotechnological methods.

Animals↗
PubMedDate not supplied

[Evolution of H3 antigen of influenza viruses isolated during 1968-1976].

Influenza viruses type A isolated in 1968--1976 were found to have changes in the content of the antigenic determinant H3. The experiments showed that while in the viruses isolated in 1968--1972 the H3 antigen was dominating, in the A/Port Chalmers/1/73 virus and some viruses isolated in 1975--1976 this antigen became more and more minor. A correlation was observed between the content of H3 antigen in viruses and the capacity of anti-H3 antiserum to inhibit the infectious activity of viruses. The prepared monospecific serum to H3 antigen contained no antibody to the other two antigenic determinants of virus or to neuraminidase and host cell antigen and was completely free from inhibitors. The serum could be used in HI, CFT, and immunodiffusion tests for the analysis of the antigenic composition of newly isolated influenza viruses.

Antigens, Viral↗
PubMedDate not supplied

[Adaptation of a Sindbis virus population to "Drosophila melanogaster" (author's transl)].

The evolution of a Sindbis virus population during serial passages in drosophila has been studied. The adaptation of Sindbis virus to this unusual host was achieved within about twenty passages. Of course, the viral population went on evolving: a thermosensitive mutant appeared which excluded the original virus; later, a new type, different in plaques morphology, was observed: it did not exclude the former type but remained balanced with it. The adaptation of Sindbis virus to drosophila was revealed in two ways: first, in an improvement of the efficiency of infection in flies without any alteration of the plating efficiency on vertebrate cells; second, in an earlier and earlier invasion of flies which resulted from an accelerated rate of early virus production by the cells. A relationship between those two modifications is suggested. The adaptation of Sindbis virus to drosophila was probably the result of a rather high number of mutationnal steps which did not involve any concomitant change in the thermosensitivity of the viral population. An interpretation is presented.

Adaptation, Physiological↗