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Results for “Genotypic diversity”

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At least 19 recordsLinked to original sources

PubMed2026

Association of Enterocytozoon bieneusi Infection with chronic/persistent diarrhea and ITS genotypic diversity: a hospital-based case-control study in Suburban Shanghai, China.

Enterocytozoon bieneusi is a globally distributed zoonotic enteric pathogen that remains largely overlooked in routine diarrheal disease surveillance. Although previous studies in Shanghai, China, have reported elevated prevalence in diarrheal populations, case-control data from suburban areas at the peri‑urban interface and the strength of the association between E. bieneusi infection and chronic diarrhea in non-immunocompromised individuals remain poorly characterized. We performed a hospital-based case-control study in suburban Shanghai, enrolling 286 diarrheal outpatients without documented immunodeficiency and 138 asymptomatic controls frequency-matched for age and sex. Fecal specimens were collected and subjected to genomic DNA extraction. E. bieneusi was detected via nested PCR amplification of the ribosomal internal transcribed spacer (ITS) region. Factors associated with infection were identified using multivariate logistic regression. Genotypic diversity and zoonotic potential were assessed by Sanger sequencing and phylogenetic analysis. The overall prevalence of E. bieneusi was 12.2% (35/286) in diarrheal patients, significantly higher than the 2.2% (3/138) observed in asymptomatic controls (P < 0.001). E. bieneusi positivity was independently associated with chronic/persistent diarrhea (adjusted odds ratio = 2.63, 95% confidence interval: 1.25-5.54, P = 0.011). Fourteen distinct ITS genotypes were identified, comprising five known genotypes (D, EbpD, SHW7, Henan-III, and CHG5) and nine novel genotypes (designated SHH2 to SHH10). Thirteen genotypes clustered within Group 1, and one genotype (CHG5) fell within Group 2, two phylogenetic groups that contain genotypes with documented zoonotic potential in global surveillance. E. bieneusi was detected at a relatively high prevalence among diarrheal patients in suburban Shanghai, and its detection was associated with chronic/persistent diarrhea. The predominance of zoonotic genotypes and the identification of nine novel Group 1 genotypes indicate phylogenetic similarity to known zoonotic lineages and warrant further investigation of local zoonotic transmission; no animal or environmental samples were analyzed in this study. These findings suggest that E. bieneusi testing may be considered as part of the differential diagnosis for patients with unexplained chronic/persistent diarrhea and highlight the need for One Health surveillance in the surveyed area.

Diarrhea↗

PubMed1992

Mode of origin and sources of genotypic diversity in triploid gynogenetic fish clones (Poeciliopsis: Poeciliidae).

Most tributaries of the Río Fuerte in northwestern Mexico contain one or more clones of allotriploid fish of the genus Poeciliopsis. We used multilocus allozyme genotypes and mitochondrial DNA (mtDNA) haplotypes to examine several potential modes of origin of these gynogenetic all-female fish. The allozyme studies corroborated earlier morphological work revealing the hybrid constitution of two triploid biotypes, Poeciliopsis 2 monacha-lucida and Poeciliopsis monacha-2 lucida. Each biotype carries one or two whole genomes from the each of the sexual species P. monacha and P. lucida. Restriction site analysis of mtDNA revealed that P. monacha was the maternal ancestor of five electrophoretically distinguishable triploid clones. Four of five clones were marked by closely related, composite, allozyme/mtDNA genotypes, suggesting they had common origins from an allodiploid clone of the P. monacha-lucida biotype. Genotypic analysis revealed that all five clones arose via the "genome addition" pathway. Fertilization of unreduced ova in P. monacha-lucida females by sperm from P. monacha and P. lucida males, respectively, gave rise to both biotypes.

Animals↗

PubMed2026

High-quality genome assembly and genotype diversity of Medicago sativa ssp. falcata.

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Letter↗

PubMed1979

Enzyme polymorphism and cyclic parthenogenesis in Daphnia magna. I. Selection and clonal diversity.

Genotype frequencies and fecundities were recorded over a period of two years for three polymorphic enzyme loci (Est, Mdh and Got) in a parthenogenetic natural population of Daphnia magna Straus (Crustacea: Cladocera). There was a large excess of heterozygotes at each locus, and some nonrandom association between loci, although 29 different three-locus genotypes were detected. There were small but significant changes in genotype frequencies that did not follow any clear seasonal cycles or overall trends, and the genotypes often differed significantly in fecundity, although the direction of the difference was not constant. These fitness differences were probably not attributable to the specific loci studied.--Models of balancing selection are of two types: segregation-balanced (e.g., heterosis) and competition-balanced (e.g., frequency dependence). Only the latter type can stabilize diversity in a clonal population. The observed selection was not heterotic, but it is not certain that it was stabilizing either. Clonal competition did not lead to victory by a single, fittest clone; genotypic diversity remained high.

Animals↗

PubMed2026

Phylogeography and molecular evolution of Newcastle disease virus across a century of global surveillance.

Newcastle disease virus (NDV) remains one of the most economically important avian pathogens worldwide, causing recurrent outbreaks in poultry despite decades of vaccination and disease control efforts. Since the first reported outbreak of NDV a hundred years ago, numerous molecular epidemiological studies have been conducted globally across diverse geographic and production settings. Following a century of NDV circulation and evolution, the present study aimed to compile all publicly available NDV sequence data and perform a comprehensive global analysis of the genetic diversity, phylogenetic relationship, and global spatiotemporal distribution of NDV over a 100-year timescale. All publicly available NDV complete genome and full-length fusion (F) gene sequences were retrieved from GenBank up to February 2026. Following rigorous quality control, phylogenetic analyses were performed based on complete genomes and F gene datasets. Phylogenetic analysis identified two genotypes within Class I and 20 genotypes within Class II NDVs, with extensive diversification at the sub-genotype level. Genotype XIII exhibited the greatest sub-genotypic diversity, while genotype VII represented the most globally disseminated genotype, reported across 36 countries. Chronological assessment based on the earliest available reports indicated an increasing number of recognized genotypes from the 1930s to recently described sub-genotypes such as XIII.2.3 and XXII.2.2. Regional diversity analysis revealed the highest genotype diversity in Western Africa, Eastern Asia, and Southern Asia. Comparative residue analysis demonstrated substantial genotype-specific variation within critical functional domains of the fusion protein, including cleavage sites, neutralizing epitopes, and heptad repeat regions. Overall, this study provides the first comprehensive 100-year global overview of NDV evolution and phylogeography. The findings highlight continuous viral diversification, broad geographic dissemination of multiple genotypes, and ongoing molecular variation, emphasizing the need for sustained genomic surveillance and periodic evaluation of vaccine compatibility with emerging NDV genotypes.

100-years of data↗

PubMed1976

The organization of genetic diversity in the parthenogenetic lizard Cnemidophorus tesselatus.

The parthogenetic lizard species Cnemidophorus tesselatus is composed of diploid populations formed by hybridization of the bisexual species C. tigris and C. septemvittatus, and of triploid populations derived from a cross between diploid tesselatus and a third bisexual species, C. sexlineatus. An analysis of allozymic variation in proteins encoded by 21 loci revealed that, primarily because of hybrid origin, individual heterozygosity in tesselatus is much higher (0.560 in diploids and 0.714 in triploids) than in the parental bisexual species (mean, 0.059). All triploid individuals apparently represent a single clone, but 12 diploid clones were identified on the basis of genotypic diversity occurring at six loci. From one to four clones were recorded in each population sampled. Three possible sources of clonal diversity in the diploid parthenogens were identified: mutation at three loci has produced three clones, each confined to a single locality; genotypic diversity at two loci apparently caused by multiple hybridization of the bisexual species accounts for four clones; and the remaining five clones apparently have arisen through recombination at three loci. The relatively limited clonal diversity of tesselatus suggests a recent origin. The evolutionary potential of tesselatus and of parthenogenetic forms in general may be less severely limited than has generally been supposed.

Alleles↗

PubMed2025

Genetic diversity of Murray Valley encephalitis virus 1951-2020 identified via phylogenetic and evolutionary analyses.

Murray Valley encephalitis virus (MVEV) is a mosquito-borne orthoflavivirus endemic to Australia that can cause fatal neurological disease. The enzootic focus of MVEV is believed to reside in northern Western Australia (WA). We sequenced whole genomes of 70 MVEV sampled over 51 years, 1969-2020, from locations across Australia and Papua New Guinea (PNG) and identified greater MVEV diversity than previously recognized. Genotype 1 (G1) demonstrated greatest intra-genotype diversity and was predominant over the sampling period with sub-lineage G1B circulating in WA and seeding activity across Australia. G1A included viruses sampled across northern WA, as well as the Northern Territory (NT). A newly identified sub-lineage G1C circulated in northern WA in 1993 and was detected again in 2003. G2 viruses were distributed across the Kimberley and Pilbara regions of northern WA, and in the NT. Although no new G3 and G4 viruses, previously identified only in PNG, were detected in the present study, other MVEV originating in PNG clustered with G1A. We confirm MVEV is enzootic in northern WA, with transmission occurring more frequently and across a wider geographical area than previously recognised. Additionally, we identify evidence of regular genotype replacement that has occurred over many decades where the major genotypes G1 and G2 have circulated in northern WA since the late 1960s. We also show that WA MVEV likely seeded an MVE outbreak in Victoria in 1974, further supporting the notion that the enzootic focus of MVEV lies in northern WA. Recent increases in MVEV detections, MVE cases and deaths in WA and across Australia highlight the need for enhanced surveillance and more frequent sampling to understand viral origin and genomic diversity, to identify potential virulence motifs, and to understand the ecological drivers that determine emergence of MVEV in northern WA and movement of MVEV across the country.

Encephalitis Virus, Murray Valley↗

PubMed2026

Molecular epidemiology and phylogeographic architecture of oncogenic intracellular bacteria in cervical cancer patients across Northern China.

BACKGROUND: Oncogenic intracellular bacteria, including Chlamydia trachomatis, Mycoplasma genitalium, and Fusobacterium nucleatum, have emerged as significant contributors to cervical carcinogenesis. Despite growing interest in microbial oncology, the molecular epidemiological landscape and phylogeographic distribution of these pathogens in Northern China remain poorly characterized. This study aimed to determine the prevalence, co-infection patterns, genotypic diversity, and spatial phylogeographic clustering of oncogenic intracellular bacteria among cervical cancer patients across five provinces of Northern China. METHODS: A cross-sectional, multi-center study was conducted between March 2022 and November 2024 across Shaanxi, Heilongjiang, Beijing, Shandong, and Inner Mongolia. Cervical swab specimens were collected from 1247 confirmed cervical cancer patients. Pathogen detection was performed using multiplex real-time polymerase chain reaction, 16S rRNA gene amplicon sequencing, and whole-genome sequencing. Phylogeographic analyses employed maximum likelihood and Bayesian evolutionary inference frameworks. Statistical analyses included multivariate logistic regression and geographic information system-based spatial clustering. RESULTS: The overall prevalence of at least one oncogenic intracellular bacterium was 68.3% (n = 852). Chlamydia trachomatis was the most prevalent pathogen detected in 41.2% of participants. Co-infection with two or more bacteria was identified in 29.7% of cases and was independently associated with advanced-stage cervical cancer (adjusted odds ratio = 2.87; 95% confidence interval: 1.94 to 4.23; p < 0.001). Phylogeographic analysis revealed three distinct molecular clades with evidence of bidirectional gene flow between Shaanxi and Heilongjiang. Whole-genome sequencing identified 14 novel virulence gene variants not previously characterized in Chinese clinical isolates. CONCLUSIONS: Oncogenic intracellular bacteria are highly prevalent and genotypically diverse among cervical cancer patients in Northern China. The identified phylogeographic clustering and novel virulence variants have direct implications for regional screening programs, targeted antimicrobial strategies, and the development of region-specific molecular diagnostic panels.

Cervical cancer↗

PubMed1991

In vitro splenic T cell responses of diverse mouse genotypes after oronasal exposure to mouse hepatitis virus, strain JHM.

Mortality rates among BALB/cByJ, A/JCr, C3H/HeSnJ, and C57BL/6NCr mice inoculated oronasally with mouse hepatitis virus (MHV) strain JHM, ranged from 25 to 67%. Spleen cells harvested from the first three genotypes at 5 days postinoculation proliferated poorly in response to concanavalin A stimulation and produced significantly less interleukin (IL) 2 than cells from uninfected control mice. The function of spleen cells harvested at 14 days postinoculation varied and was host genotype-dependent. Despite clinical signs among some infected C57BL/6NCr mice, spleen cell function was relatively unaffected. C57BL/10ScNCr, B10.A, and SJL/JCr mice remained clinically normal after MHV inoculation. Proliferation and IL2 production by cells from inoculated C57BL/10ScNCr and B10.A mice were similar to responses of their respective controls. In contrast, cells from inoculated SJL/JCr mice were hyper-responsive and produced peak levels of IL2 earlier than control cells. Among the seven genotypes tested, only BALB/cByJ and C3H/HeSnJ spleen cells produced detectable IL4 after primary stimulation with concanavalin A or after priming and restimulation. Primary IL4 production by cells from these two genotypes was significantly reduced if donors were inoculated with MHV 5 days prior to spleen harvest. IL4 production by cells from acutely infected BALB/cByJ mice was considerably enhanced by priming and restimulation.

Administration, Intranasal↗

PubMed2026

Convergent IGF2 overexpression in pheochromocytoma/paraganglioma: insights from Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth and tumor predisposition, caused by dysregulated expression of genes on chromosome 11p15.5. An association between BWS and pheochromocytoma/paraganglioma (PPGL) has been suggested in isolated case reports over the past fifty years, but the molecular basis for this link remains unclear. We identified four patients with BWS who developed metastatic PPGL and investigated IGF2 pathway activation in these tumors and in PPGL across various genotypes. Pan-cancer transcriptomic analysis of The Cancer Genome Atlas (TCGA) demonstrated that PPGL overexpresses IGF2, with pseudohypoxic tumors exhibiting higher expression compared to other molecular clusters. Loss of heterozygosity and loss of imprinting at 11p15.5 partially explain this overexpression, with PPGL additionally demonstrating globally elevated expression of imprinted genes compared to most other tumor types, suggesting a broader relaxation of genomic imprinting. Cognate receptor profiling revealed that PPGLs are equipped to respond to IGF2 signaling, with high expression of IGF1R and insulin receptor isoform A (IR-A). Immunohistochemistry confirmed IGF2 protein overexpression in both BWS-associated and genotypically diverse sporadic PPGLs. Our results indicate that IGF2 overexpression is a convergent molecular feature of PPGL across genotypes and suggest the IGF2 pathway as a potential diagnostic and therapeutic target.

Humans↗

PubMed1992

Clonal structure of the introduced freshwater snail Potamopyrgus antipodarum (Prosobranchia: Hydrobiidae), as revealed by DNA fingerprinting.

Multi-locus DNA fingerprints were obtained from individuals of the hydrobiid snail, Potamopyrgus antipodarum (= P. jenkinsi), by using an RNA derivative (pSPT 18.15) of Jeffrey's 33.15 minisatellite core sequence. Whole-body homogenization of snails yielded 3.21 +/- 0.09 micrograms DNA per individual, producing complex profiles comprising 12-22 fragments within the 1.0-20.0 kilobase (kb) size range. Fingerprints from natural and experimental populations identified three distinct clonal genotypes corresponding to morphological strains A, B and C, with only rare mutational variants. Mother-offspring comparisons of genetic fingerprints revealed genetic stability during apomictic parthenogenesis. Data support the notion that British populations of P. antipodarum comprise three widespread obligate parthenogenetic clones resulting from a mid-19th Century introduction from Australasia. The present-day low levels of genotypic diversity are discussed in relation to the typical occurrence of P. antipodarum in man-made or immature habitats.

Animals↗

PubMed2026

In-host adaptation of Staphylococcus aureus during recurrent prosthetic joint infections: a retrospective longitudinal study.

UNLABELLED: The aim of this study was to characterize the in vivo evolution of Staphylococcus aureus strains involved in recurrent prosthetic joint infections (PJIs) both phenotypically and genomically. We conducted a monocentric retrospective study in a 1,437-bed French teaching hospital between 2013 and 2021. All patients presenting a recurrent S. aureus-related PJI-defined as at least two strains isolated from distinct clinical samples more than 90 days apart-of the knee, hip, or shoulder were included. Clinical data were reviewed, and all isolates underwent phenotypic characterization, including antimicrobial susceptibility testing, growth rate determination, biofilm production assays, metabolic profiling (API 50 CH), and virulence evaluation using the Galleria mellonella infection model. Whole-genome sequencing (WGS) was performed for all strains, followed by analyses of core-genome multilocus sequence typing (cgMLST), resistome, virulome, and mobilome composition, and single-nucleotide polymorphisms (SNPs). Thirteen patients met inclusion criteria, yielding 55 S. aureus isolates. Eight patients experienced recurrent infections caused by genetically closely related strains throughout the clinical course (median: three strains per patient; range: 2-6), whereas five patients were infected by genetically distinct strains. At baseline, isolates were genetically diverse and susceptible to methicillin and rifampicin; two showed fluoroquinolone resistance due to grlA and/or gyrA mutations. In one patient (patient C), a recurrent isolate acquired an rpoB S486L mutation, conferring rifampicin resistance after rifampicin exposure. Due to the limited sample size, it is difficult to draw definitive conclusions from the phenotypic analyses. This study highlights the adaptive evolution of S. aureus during chronic PJIs and underscores the need for further research to better understand intra-host dynamics in long-standing infections. IMPORTANCE: This study conducted in a 1,437-bed French teaching hospital analyzed the genomic and phenotypic evolution of 55 Staphylococcus aureus strains recovered in recurrent PJIs from 13 patients. The first strains showed high genotypic diversity across 12 different sequence types. Among the 13 patients, only eight experienced a true recurrence with the same strain, while five were contaminated with a different strain of S. aureus, indicating a new infection. Moreover, this study underscores the complex within-host evolution of S. aureus and highlights the phenotypical and genotypical adaptation during chronic infection.

Staphylococcus aureus↗

PubMed2026

[Analysis of clinical spectrum and genotype characteristics of 9 cases of Fabry disease].

Objective: To investigate the genetic characteristics and clinical phenotypes across different genotypes in patients with Fabry disease. Methods: Clinical data of 9 confirmed FD patients treated from June 2019 to December 2025 at the Affiliated Huai'an No.1 people's Hospital of Nanjing Medical University were retrospectively analyzed. The diagnostic criteria for FD included α-galactosidase A (α-GalA) activity, GLA gene sequencing, globotriaosylsphingosine levels, and renal biopsy findings, supplemented by clinical symptoms and signs. Genetic testing was performed on both the proband and their family members. Proband underwent next-generation sequencing of the GLA gene using the long-range PCR. Family members were verified by conventional PCR combined with Sanger sequencing. Variants were classified according to the 2015 American College of Medical Genetics and Genomics guidelines for sequence variation interpretation. Results: Of the 9 patients, 4 were males and 5 were females. The mean α-Gal A activity was (0.47±0.13) μmol·L-1·h-1 in males and (2.38±0.91) μmol·L-1·h-1 in females. The mean age at diagnosis was (43.0±16.7) years. The main clinical manifestations included renal impairment in 7 cases (proteinuria, chronic kidney disease, or end-stage renal disease), cardiac involvement in 8 cases (myocardial hypertrophy, arrhythmia, etc.), and autonomic nervous system symptoms in 6 cases (hypohidrosis). Pathogenic or likely pathogenic GLA variants were identified in all 9 patients, of which 8 were classified as pathogenic and 1 as a variant of uncertain significance. Three patients underwent family screening: in one case, the variant was possibly inherited from the maternal grandmother; one case was confirmed as a de novo mutation; and in one case, paternal inheritance could not be excluded. Renal biopsy in one patient revealed characteristic myeloid bodies and zebra bodies. Among the 9 patients, 1 received agalsidase α and 8 received agalsidase β, with one case developing infusion-associated reactions after 12 infusions. During the follow-up period, one patient died due to cardiac complications. Conclusions: FD patients exhibit a broad clinical spectrum and diverse genotypes. Atypical presentations should be closely monitored to enable early diagnosis and treatment, thereby improving prognosis.

Humans↗

PubMed2025

Clinical Impact and Genetic Analysis of Enteric Viruses Associated With Acute Gastroenteritis in Greater Accra, Ghana: A Comprehensive Study of Five Viruses.

Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus-specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score > 7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.

Humans↗

PubMed2026

Dissecting genetic architecture of growth and yield traits in horsegram using GWAS.

Horsegram (Macrotyloma uniflorum), a member of the Fabaceae family, is a nutritious and low-cost legume used for both grain and fodder. This study employed a genome-wide association approach to identify loci linked to key agronomic traits in horsegram. Plant height, seed size, and shoot fresh weight were evaluated in a panel of 96 diverse genotypes. GBS was performed using the Illumina HiSeq platform, yielding 20,241 high-quality SNPs after filtering at a 5% minor allele frequency. Population structure analysis classified genotypes into three admixed subgroups. Phenotyping was conducted over three consecutive years at two locations in Himachal Pradesh (Palampur and Bajaura) using a randomized block design with two replications. GWAS analyses using GLM, MLM, FarmCPU, and BLINK models identified eight markers for plant height, three for seed size, and five for shoot fresh weight across different chromosomes. These markers provide valuable tools for accelerating trait improvement in future horsegram breeding programs.

Genome-Wide Association Study↗

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↗

PubMed1992

Large, identical, tandem repeating units in the C protein alpha antigen gene, bca, of group B streptococci.

Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in the United States. The surface-associated C protein alpha antigen of GBS is thought to have a role in both virulence and immunity. We previously cloned the C protein alpha antigen structural gene (named bca for group B, C protein, alpha) into Escherichia coli. Western blots of both the native alpha antigen and the cloned gene product demonstrate a regularly laddered pattern of heterogeneous polypeptides. The nucleotide sequence of the bca locus reveals an open reading frame of 3060 nucleotides encoding a precursor protein of 108,705 Da. Cleavage of a putative signal sequence of 41 amino acids yields a mature protein of 104,106 Da. The 20,417-Da N-terminal region of the alpha antigen shows no homology to previously described protein sequences and is followed by a series of nine tandem repeating units that make up 74% of the mature protein. Each repeating unit is identical and consists of 82 amino acids with a molecular mass of 8665 Da, which is encoded by 246 nucleotides. The size of the repeating units corresponds to the observed size differences in the heterogeneous ladder of alpha C proteins expressed by GBS. The C-terminal region of the alpha antigen contains a membrane anchor domain motif that is shared by a number of Gram-positive surface proteins. The large region of identical repeating units in bca defines protective epitopes and may play a role in generating phenotypic and genotypic diversity of the alpha antigen.

Amino Acid Sequence↗

PubMed2025

Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans.

Fungi can cause devastating invasive infections, typically in immunocompromised patients. Treatment is complicated both by the evolutionary similarity between humans and fungi and by the frequent emergence of drug resistance. Studies in fungal pathogens have long been slowed by a lack of high-throughput tools and community resources that are common in model organisms. Here we demonstrate a high-throughput transposon mutagenesis and sequencing (TN-seq) system in Cryptococcus neoformans that enables genome-wide determination of gene essentiality. We employed a random forest machine learning approach to classify the C. neoformans genome as essential or nonessential, predicting 1,465 essential genes, including 302 that lack human orthologs. These genes are ideal targets for new antifungal drug development. TN-seq also enables genome-wide measurement of the fitness contribution of genes to phenotypes of interest. As proof of principle, we demonstrate the genome-wide contribution of genes to growth in fluconazole, a clinically used antifungal. We show a novel role for the well-studied RIM101 pathway in fluconazole susceptibility. We also show that insertions of transposons into the 5' upstream region can drive sensitization of essential genes, enabling screenlike assays of both essential and nonessential components of the genome. Using this approach, we demonstrate a role for mitochondrial function in fluconazole sensitivity, such that tuning down many essential mitochondrial genes via 5' insertions can drive resistance to fluconazole. Our assay system will be valuable in future studies of C. neoformans, particularly in examining the consequences of genotypic diversity.

Cryptococcus neoformans↗