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PubMed2000

Characterization of plasmid-borne and chromosome-encoded traits of Agrobacterium biovar 1, 2, and 3 strains from France.

We collected 111 Agrobacterium isolates from galls of various origins (most of them from France) and analyzed both their plasmid-borne and chromosome-encoded traits. Phenotypic analysis of these strains allowed their classification in three phena which exactly matched the delineation of biovars 1, 2, and 3. A fourth phenon was identified which comprises three atypical strains. The phenotypic analysis has also allowed us to identify 12 additional characteristics which could be used to identify the three biovars of Agrobacterium. Our results also suggest that biovar 1 and 2 represent distinct species. Analysis of plasmid-borne traits confirmed that tartrate utilization is a common feature of biovar 3 strains (now named Agrobacterium vitis) and of Agrobacterium grapevine strains in general. Among pathogenic strains of Agrobacterium, several exhibited unusual opine synthesis and degradation patterns, and one strain of biovar 3 induced tumors containing vitopine and a novel opine-like molecule derived from putrescine. We have named this compound ridéopine.

Chromosome Mapping↗
PubMed2004

Mouse models of atopic eczema critically evaluated.

Atopic eczema (AE) is a chronic relapsing inflammatory skin disorder with increasing prevalence in Western societies. Even though we have made considerable progress in understanding the cellular and molecular nature of cutaneous inflammation, the precise pathomechanisms of AE still remain elusive. Experimental animal models are indispensable tools to study the pathogenic mechanisms and to test novel therapeutic approaches in vivo. For AE a considerable number of mouse models have been proposed and have been used to study specific aspects of the disease, such as genetics, skin barrier defects, immune deviations, bacteria-host interactions or the role of cytokines or chemokines in the inflammatory process. While some models closely resemble human AE, others appear to reflect only specific aspects of the disease. Here we review the currently available mouse models of AE in light of the novel World Allergy Organization classification of eczematous skin diseases and evaluate them according to their clinical, histopathological and immunological findings. The pathogenetic analogies between mice and men will be discussed.

Animals↗
PubMed2022

A deep learning approach to real-time HIV outbreak detection using genetic data.

Pathogen genomic sequence data are increasingly made available for epidemiological monitoring. A main interest is to identify and assess the potential of infectious disease outbreaks. While popular methods to analyze sequence data often involve phylogenetic tree inference, they are vulnerable to errors from recombination and impose a high computational cost, making it difficult to obtain real-time results when the number of sequences is in or above the thousands. Here, we propose an alternative strategy to outbreak detection using genomic data based on deep learning methods developed for image classification. The key idea is to use a pairwise genetic distance matrix calculated from viral sequences as an image, and develop convolutional neutral network (CNN) models to classify areas of the images that show signatures of active outbreak, leading to identification of subsets of sequences taken from an active outbreak. We showed that our method is efficient in finding HIV-1 outbreaks with R0 ≥ 2.5, and overall a specificity exceeding 98% and sensitivity better than 92%. We validated our approach using data from HIV-1 CRF01 in Europe, containing both endemic sequences and a well-known dual outbreak in intravenous drug users. Our model accurately identified known outbreak sequences in the background of slower spreading HIV. Importantly, we detected both outbreaks early on, before they were over, implying that had this method been applied in real-time as data became available, one would have been able to intervene and possibly prevent the extent of these outbreaks. This approach is scalable to processing hundreds of thousands of sequences, making it useful for current and future real-time epidemiological investigations, including public health monitoring using large databases and especially for rapid outbreak identification.

Humans↗
PubMed1997

Human papillomaviruses: a study of their prevalence in the epithelial hyperplastic lesions of the larynx.

This study investigated the prevalence of human papillomavirus (HPV) infection in various laryngeal epithelial hyperplastic lesions using the Kambic classification from simple hyperplasia to invasive squamous cell carcinoma. For detection of HPV infection polymerase chain reaction (PCR) with 3 different HPV consensus primer sets and in situ hybridization were used. The presence of the HPV DNA was detected in only 2 of the 88 specimens tested: HPV type 6 was detected in 1 case of simple hyperplasia and HPV type 16 in 1 case of invasive squamous cell carcinoma. In conclusion, our study suggests that most laryngeal epithelial hyperplastic lesions are not associated with HPV infection and that other pathogenic mechanisms are more important in the etiology of these lesions.

Carcinoma, Squamous Cell↗
PubMed2005

Phylogenetic relationships between members of the crucifer pathogenic Leptosphaeria maculans species complex as shown by mating type (MAT1-2), actin, and beta-tubulin sequences.

The dothideomycetous fungus Leptosphaeria maculans comprises a complex of species differing in specificity and pathogenicity on Brassica napus. Twenty-eight isolates were investigated and compared to 20 other species of the Pleosporales order. Sequences of the mating type MAT1-2 (23), fragments of actin (48) and beta-tubulin (45) genes were determined and used for phylogenetic analyses inferred by maximum parsimony, distance, maximum likelihood, and Bayesian approaches. These different approaches using single genes essentially confirmed findings using concatanated sequences. L. maculans formed a monophyletic group separate from Leptosphaeria biglobosa. The L. biglobosa clade encompasses five sub-clades; this finding is consistent with classification made previously on the basis of internal-transcribed sequences of the ribosomal DNA repeat. The propensity for purifying and neutral evolution of the three genes was determined using sliding window analysis, a technique not previously applied to genes of filamentous fungi. For members of the L. maculans species complex, this approach showed that in comparison to actin and beta-tubulin, exonic sequences of MAT1-2 were more diverse and appeared to evolve at a faster rate. However, different regions of MAT1-2 displayed different degrees of sequence conservation. The more conserved upstream region (including the High Mobility Group domain) may be better suited for interspecies differentiation, while the more diverse downstream region is more appropriate for intraspecies comparisons.

Actins↗
PubMed2003

Characterizing T-cell receptor gamma-variable gene in Aotus nancymaae owl monkey peripheral blood.

Gammadelta T lymphocytes have a heterodimeric complex formed by the association of gamma and delta chains as receptor. Proliferation of this lymphocyte population has been observed, when infection by several pathogens such as Mycobacterium tuberculosis and Plasmodium spp. occurs. The New World Monkey Aotus nancymaae has become a very good experimental model for the immunological and physiopathological study of these infectious agents. The A. nancymaae gamma-variable region was characterized from peripheral blood samples by using cDNA and genomic DNA polymerase chain reaction amplification, DNA sequencing, and dot-blot hybridization techniques. Seventeen different T-cell receptor gamma-variable (TCRGV) sequences were obtained. These sequences were distributed among TCRGV subsets 1, 2, or 3, according to human subset classification. Although no subset 4 amplification was obtained, this subset was detected by dot-blot hybridization. The presence of these 4 subsets resembles the behavior displayed by 'gammadelta-low species' (humans and mice), where high diversity among these lymphocytes can be observed. Homologies greater than 70% were found with respect to humans. Sequence convergence between human and A. nancymaae subsets 1 and 3 highlights Aotus as a promising model for studying these lymphocyte functions.

Amino Acid Sequence↗
PubMed2003

A molecular perspective on corneal dystrophies.

Corneal dystrophies refer to a group of corneal diseases and that are genetically determined. These have been traditionally classified with respect to the layer of cornea involved. We now know that this does not reflect the underlying pathobiology. Most of the corneal dystrophies are of Mendelian inheritance with some phenotype diversity and a variable degree of penetrance. The dystrophies involving enzymatic processes tend to be of autosomal recessive inheritance. In some cases, such as keratoconus, the inheritance pattern is not always clear and is considered complex. The age of onset of the disease, as in most inherited eye disorders, is variable and does not reflect the underlying pathogenic defect. Few cases are congenital. Our understanding of corneal dystrophies is undergoing somewhat of a revolution as over 12 chromosomes have been associated with corneal dystrophies with mutations identified in at least 14 genes if one includes anterior segment dysgenesis in this group of conditions. Several dystrophies remain without a gene or a genetic location (locus) and more familial studies are required. The new molecular information is challenging the traditional thinking about these conditions that was usually guided by the histopathological findings. As this new knowledge becomes more refined, the classification of this group of disorders will eventually be revisited to have a molecular basis. The elucidation of the underlying biochemical pathways may allow us to envisage the possibility of modulating these phenotypes in the future.

Corneal Dystrophies, Hereditary↗
PubMed2002

Severity of angina pectoris and risk of ischemic stroke.

BACKGROUND AND PURPOSE: Ischemic stroke and coronary heart disease (CHD) share risk factors and pathogenic process, ie, atherosclerosis and thrombosis. We examined the relationship between severity of angina pectoris and its accompanying characteristics and the risk of incident ischemic stroke. METHODS: We traced 3122 patients with stable CHD, included in a secondary prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial. CHD was documented by a history of myocardial infarction > or =6 months and < 5 years before enrollment and/or stable angina pectoris with evidence of ischemia confirmed by ancillary diagnostic testing. Severity of angina pectoris was assessed according to the Canadian Cardiovascular Society angina classification, and heart failure functional class according to the New York Heart Association (NYHA) classification. Patients with severe heart failure or unstable angina on enrollment were excluded. RESULTS: During a mean follow-up period of 8.2 years, 186 patients developed an ischemic stroke. The cumulative rate of ischemic stroke increased in a dose-response manner from 4.7% in patients with no angina to 5.7%, 8.4%, and 12.9% in patients with angina classes 1, 2, and 3, respectively (P<0.001). Patients with NYHA functional class 1 had a 5.5% rate of ischemic stroke versus 7.3% and 9.6% in patients with classes 2 and 3, respectively (P=0.05). In a Cox proportional-hazard model adjusting for conventional risk factors and potential confounders, the hazard ratio associated with angina class 1 was 1.20 (95% CI, 0.83 to 1.74); class 2, 1.66 (95% CI, 1.12 to 2.45); and class 3, 2.35 (95% CI, 1.08 to 5.13), as compared with patients with no angina. Hazard ratios of ischemic stroke associated with conventional risk factors were 1.55 for a 10-year age increment, 2.16 for diabetes mellitus, 1.81 for current smoking, and 1.29 for a 20 mm Hg increase in systolic blood pressure. CONCLUSIONS: Severity of angina pectoris in patients with stable CHD predicts an increased risk of subsequent ischemic stroke. The association between angina class and incident ischemic stroke is independent of traditional vascular risk factors.

Aged↗
PubMed1995

Wegener's granulomatosis.

Since its first description by Wegener in 1936, Wegener's granulomatosis has undergone significant changes in terms of clinical scope, diagnosis, and treatment. It is no longer tenable to insist on the fulfillment of the Wegener's triad to make the diagnosis. The wide range of clinical presentations is encompassed by the ELK (ear, nose, and throat; lung; kidney) classification in which any combination or singular involvement of the major sites can be considered within the Wegener's spectrum if supported by the appropriate pathologic findings or the presence of a cytoplasmic antineutrophil cytoplasmic antibody pattern. Treatment is based on the extent of involvement and clinical tempo. Trimethoprim-sulfamethoxazole may be used for patients with localized disease. Systemic disease, including involvement of the kidney, mononeuritis multiplex, and skin vasculitis, is treated with systemic glucocorticoids and cyclophosphamide. Research into the antineutrophil cytoplasmic antibody phenomenon is yielding new insights into possible pathogenic mechanisms.

Granulomatosis with Polyangiitis↗
PubMed2003

Impact of genotypic studies on mycobacterial taxonomy: the new mycobacteria of the 1990s.

The advancement of genetic techniques has greatly boosted taxonomic studies in recent years. Within the genus Mycobacterium, 42 new species have been detected since 1990, most of which were grown from clinical samples. Along with species for which relatively large numbers of strains have been reported, some of the new species of mycobacteria have been detected rarely or even only once. From the phenotypic point of view, among the new taxa, chromogens exceed nonchromogens while the numbers of slowly and rapidly growing species are equivalent. Whereas conventional identification tests were usually inconclusive, an important role was played by lipid analyses and in particular by high-performance liquid chromatography. Genotypic investigations based on sequencing of 16S rRNA gene have certainly made the most important contribution. The investigation of genetic relatedness led to the redistribution of the species previously included in the classically known categories of slow and rapid growers into new groupings. Within slow growers, the intermediate branch related to Mycobacterium simiae and the cluster of organisms related to Mycobacterium terrae have been differentiated; among rapid growers, the group of thermotolerant mycobacteria has emerged. The majority of species are resistant to isoniazid and, to a lesser extent, to rifampin. Many of the new species of mycobacteria are potentially pathogenic, and there are numerous reports of their involvement in diseases. Apart from disseminated and localized diseases in immunocompromised patients, the most frequent infections in immunocompetent people involve the lungs, skin, and, in children, cervical lymph nodes. The awareness of such new mycobacteria, far from being a merely speculative exercise, is therefore important for clinicians and microbiologists.

Bacterial Proteins↗
PubMed1987

[Recent trend of childhood bacterial meningitis in Japan (1979-1984). Part 4. A classification of prognosis and antibiotic treatment based on causative agents].

Nine hundred seventy cases of childhood bacterial meningitis treated at 107 institutions in Japan from 1979 through 1984 were studied using questionnaire. The number of cases that underwent antimicrobial monotherapy remained nearly constant during the study period, but cases of therapies with beta-lactam combined with aminoglycosides (AGs) decreased in number and a gradual increase in the use of beta-lactam combined with non-AGs antibiotics including beta-lactam (Non AGs) was observed. A trend showing decrease in case fatality rate (CFR) was observed except that CFR for Gram-positive bacterial infections treated with beta-lactam + AGs remained at a same level. Cases treated with antibiotics were classified into 3 groups according to major etiological pathogens. Cases with Staphylococcus aureus gave a poor prognosis, among 27 total cases, CFR was 28.6% (2/7) with monotherapy, 50.0% (6/12) with beta-lactam + AGs and 37.5% (3/8) with beta-lactam + Non AGs (P less than 0.1). Among 100 cases of group B Streptococcus (GBS), CFR was 20.0% as a whole, 17.3% (9/52) for monotherapy and 34.5% (10/29) for beta-lactam + AGs (P less than 0.1). Among 198 cases of Streptococcus pneumoniae, CFR was 12.1% as a whole, and was 12.3% (18/146) with monotherapy. CFR for the cases treated with beta-lactam + AGs was 20.8% (5/24) and with beta-lactam + Non AGs was 3.6% (1/28) (P less than 0.1). CFR for 292 cases of Haemophilus influenzae meningitis was fairly low, and was 6.1% (9/148) with monotherapy, 7.4% (5/68) with beta-lactam + AGs and 3.9% (3/76) with beta-lactam + Non AGs, thus very slight differences were observed among the 3 groups of treatment. Among 111 cases of Escherichia coli, monotherapy and beta-lactam + Non AGs gave 6.5% (2/31) CFR, and 5.6% (1/18) CFR, respectively, whereas beta-lactam + AGs showed CFR of 19.4% (12/62), demonstrating a significant difference tendency (P less than 0.1). Similar tendencies were observed in the cases of Listeria monocytogenes, Proteus mirabilis, Pseudomonas aeruginosa and Enterococcus faecalis. Contrary to the high CFR observed with the beta-lactam + AGs treatment, significantly low CFR was frequently obtained in cases treated with a combination of penicillins with cephalosporins including latamoxef or beta-lactam with chloramphenicol. Infections with GBS, E. coli, and P. mirabilis occurred largely in the age between 0 to 6 months and CFR was especially high in the very young.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed2026

Metabolic engineering of Candida yeasts for biotechnological applications.

Candida yeasts represent a versatile yet underexploited platform for industrial biotechnology. These yeasts utilize a remarkably broad range of carbon sources, particularly for hydrophobic carbon sources, coupled with robust growth and diverse biosynthetic capacities, making them promising hosts for sustainable production of chemicals, fuels, and proteins. Despite these advantages, industrial deployment of Candida species has been hindered by concerns regarding opportunistic pathogenicity and the historical lack of efficient genetic manipulation tools, leading to a substantial gap between metabolic potential and practical utilization. Recent advances in functional genomics, genome editing, and systems metabolic engineering are rapidly overcoming these barriers, enabling more precise and efficient strain development. In this review, we systematically summarize recent progress in the metabolic engineering of Candida species as microbial cell factories, with particular emphasis on expanding genetic toolkits, utilizting renewable and non-conventional carbon sources, and biosynthesizing high-value compounds. In addition, we propose a biosafety-oriented classification framework to support their safe industrial deployment. Finally, we discuss current challenges and emerging opportunities, emphasizing that the synergy of synthetic biology and artificial intelligence-driven design holds the key to unlocking the biotechnological potential of Candida yeasts.

Candida↗
PubMed1982

Genetic vulnerability for depression and life events.

In the last decades there has been an increased interest in studies of life events and depression. Although evidence has accumulated suggesting that life events might be relevant for the occurrence and development of depression, their pathogenic role is still poorly understood. In the present study, we have investigated whether a possible interaction exists between external events and biological vulnerability for depression. On the basis of an intensive family study, 128 depressed patients, consecutively admitted to the department of psychiatry of Umeå University Hospital have been divided into 2 groups, those suffering from 'depression pure disease' (i.e. those with a family loading for affective disorders, n = 48) and, those suffering from 'depression sporadic disease' (i.e. those without any heredity for affective disorders, n = 80) according to Winokur's classification. The occurrence of life events has been assessed in each patient by means of a semistructured interview. The mean number of events experienced by the patients in the two groups proved to be similar during the different time periods taken into account, and the mean number of events per patient was similar to that found by other authors who studied life events and depression. None of the categorizations used to group the life events discriminated between the groups. It is concluded from this study that genetic vulnerability for depression does not enhance an individual's vulnerability for stressful events.

Adult↗
PubMed2026

A novel missense mutation in tropomyosin 1 gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder that can lead to heart failure or sudden death. Family-based identification of rare sarcomeric variants can support molecular diagnosis and cascade screening in inherited HCM. This study aimed to identify and evaluate a novel TPM1 variant found in a Vietnamese family with HCM. The proband, a 3-year-old boy diagnosed with HCM, and eight relatives from three generations underwent clinical and genetic evaluation. A candidate variant initially identified by targeted next-generation sequencing was validated by PCR and Sanger sequencing. Familial segregation analysis was performed, and variant pathogenicity was assessed according to ACMG guidelines with support from in silico prediction and structural modeling. Sanger sequencing confirmed a heterozygous missense variant in exon 6 of TPM1 NM_001018005.2:c.576G&#xa0;>&#xa0;C, p.(Glu192Asp), in the proband, his father, and paternal grandfather, all of whom exhibited clinical signs of HCM. The variant was absent in unaffected relatives and in public population databases. Based on ACMG criteria (PM1, PM2, PM5, and PP3), the variant was classified as likely pathogenic. This novel TPM1 variant segregated with HCM in a Vietnamese family, expands the known mutational spectrum of TPM1 in hypertrophic cardiomyopathy, and warrants further functional investigation and familial genetic evaluation.

American College of Medical Genetics and Genomics ↗
PubMed2006

MannDB - a microbial database of automated protein sequence analyses and evidence integration for protein characterization.

BACKGROUND: MannDB was created to meet a need for rapid, comprehensive automated protein sequence analyses to support selection of proteins suitable as targets for driving the development of reagents for pathogen or protein toxin detection. Because a large number of open-source tools were needed, it was necessary to produce a software system to scale the computations for whole-proteome analysis. Thus, we built a fully automated system for executing software tools and for storage, integration, and display of automated protein sequence analysis and annotation data. DESCRIPTION: MannDB is a relational database that organizes data resulting from fully automated, high-throughput protein-sequence analyses using open-source tools. Types of analyses provided include predictions of cleavage, chemical properties, classification, features, functional assignment, post-translational modifications, motifs, antigenicity, and secondary structure. Proteomes (lists of hypothetical and known proteins) are downloaded and parsed from Genbank and then inserted into MannDB, and annotations from SwissProt are downloaded when identifiers are found in the Genbank entry or when identical sequences are identified. Currently 36 open-source tools are run against MannDB protein sequences either on local systems or by means of batch submission to external servers. In addition, BLAST against protein entries in MvirDB, our database of microbial virulence factors, is performed. A web client browser enables viewing of computational results and downloaded annotations, and a query tool enables structured and free-text search capabilities. When available, links to external databases, including MvirDB, are provided. MannDB contains whole-proteome analyses for at least one representative organism from each category of biological threat organism listed by APHIS, CDC, HHS, NIAID, USDA, USFDA, and WHO. CONCLUSION: MannDB comprises a large number of genomes and comprehensive protein sequence analyses representing organisms listed as high-priority agents on the websites of several governmental organizations concerned with bio-terrorism. MannDB provides the user with a BLAST interface for comparison of native and non-native sequences and a query tool for conveniently selecting proteins of interest. In addition, the user has access to a web-based browser that compiles comprehensive and extensive reports. Access to MannDB is freely available at http://manndb.llnl.gov/.

Algorithms↗
PubMed2002

Correlation between the renal C1q deposition and serum anti-C1q antibody: a potential role of anti-C1q antibody in lupus nephritis.

The anti-C1q antibody has been shown to be associated with lupus patients with renal involvement. We conducted a study to determine the relationship between the serum anti-C1q titer and the renal deposition of C1q. The serum anti-C1q was measured in 26 healthy controls and 47 systemic lupus erythematosus (SLE) patients who were divided into 2 groups as non-nephritis and nephritis SLE. We analyzed the relationship between the anti-C1q titers and SLE, renal C1q staining and the WHO classification for lupus nephritis. The result revealed that the serum anti-C1q was present in 50.8% of the SLE patients, that its levels in those with renal involvement were significantly higher than in the normal control group (61.540 +/- 87.720 U/ml vs 15.750 +/- 2.530 U/ml, p = 0.005). Besides, the serum anti-C1q levels were higher in the patients with lupus nephritis with C1q deposition in the kidney tissue (66.038 +/- 91.141 U/ml vs 16.652 +/- 3.097 U/ml, p < 0.01). There seems to be evidence supporting that the autoantibody anti-C1q might play a pathogenic role in lupus nephritis.

Adult↗
PubMed2006

HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin.

OBJECTIVE: Familial autosomal dominant frontotemporal dementia with ubiquitin-positive, tau-negative inclusions in the brain linked to 17q21-22 recently has been reported to carry null mutations in the progranulin gene (PGRN). Hereditary dysphasic disinhibition dementia (HDDD) is a frontotemporal dementia with prominent changes in behavior and language deficits. A previous study found significant linkage to chromosome 17 in a HDDD family (HDDD2), but no mutation in the MAPT gene. Longitudinal follow-up has enabled us to identify new cases and to further characterize the dementia in this family. The goals of this study were to develop research criteria to classify the different clinical expressions of dementia observed in this large kindred, to identify the causal mutation in affected individuals and correlate this with phenotypic characteristics in this pedigree, and to assess the neuropathological characteristics using immunohistochemical techniques. METHODS: In this study we describe a detailed clinical, pathological and mutation analysis of the HDDD2 kindred. RESULTS: Neuropathologically, HDDD2 represents a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U). We developed research classification criteria and identified three distinct diagnostic thresholds, which helped localize the disease locus. The chromosomal region with the strongest evidence of linkage lies within the minimum critical region for FTLD-U. Sequencing of each exon of the PGRN gene led to the identification of a novel missense mutation, Ala-9 Asp, within the signal peptide. INTERPRETATION: HDDD2 is an FTLD-U caused by a missense mutation in the PGRN gene that cosegregates with the disease and with the disease haplotype in at-risk individuals. This mutation is the first reported pathogenic missense mutation in the signal peptide of the PGRN gene causing FTLD-U. In light of the previous reports of null mutations and its position in the gene, two possible pathological mechanisms are proposed: (1) the protein may accumulate within the endoplasmic reticulum due to inefficient secretion; and (2) mutant RNA may have a lower expression because of degradation via nonsense-mediated decay.

Adult↗
PubMed2004

Comparison of four regions in the replicase gene of heterologous infectious bronchitis virus strains.

Infectious bronchitis virus (IBV) produces six subgenomic (sg) mRNAs, each containing a 64 nucleotide (nt) leader sequence, derived from the 5' end of the genome by a discontinuous process. Several putative functional domains such as a papain-like proteinase (PL(pro)), main protease (M(pro)), RNA-dependent RNA polymerase (RdRp), and RNA helicase encoded by the replicase gene are important for virus replication. We have sequenced four regions of the replicase genes corresponding to the 5'-terminal sequence, PL(pro), M(pro), and RdRp domains from 20 heterologous IBV strains, and compared them with previously published coronavirus sequences. All the coronavirus 5'-termini and PL(pro) domains were divergent, unlike the M(pro) and the RdRp domains that were highly conserved with 28% and 48% conserved residues, respectively. Among IBV strains, the 5' untranslated region including the leader sequence was highly conserved (>94% identical); whereas, the N-terminal coding region and the PL(pro) domains were highly variable ranging from 84.6% to 100%, and 77.6% to 100% identity, respectively. The IBV M(pro) and RdRp domains were highly conserved with 82.7% and 92.7% conserved residues, respectively. The BJ strain was the most different from other IBVs in all four regions of the replicase. Phylogeny-based clustering based on replicase genes was identical to the antigen-based classification of coronaviruses into three groups. However, the IBV strain classification based on replicase gene domains did not correlate with that of the type-specific antigenic groups. The replicase gene sequences of many IBVs recovered from infected chickens were identical to those of vaccine viruses irrespective of serotype, suggesting that either there has been an exchange of genetic material among vaccine and field isolates or that there is a convergent evolution to a specific replicase genotype. There was no correlation between the genotype of any region of the replicase gene and pathotype, suggesting that the replicase is not the sole determinant of IBV pathogenicity.

5' Untranslated Regions↗