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At least 1,009 records · Page 56Linked to original sources
PubMed2005

High level of hepatitis B virus DNA after HBeAg-to-anti-HBe seroconversion is related to coexistence of mutations in its precore and basal core promoter.

AIM: G1896A mutation in precore or A1762T/G1764A mutations in basal core promoter are suspected to be responsible for patients with detectable level of HBV DNA in serum after seroconversion from HBeAg to anti-HBe. However, G1896A variant has impaired, while A1762T/G1764A variant may have intact replication ability. They themselves or their coexistence status may play different roles in such meaningless seroconversion. For these reasons, the significances of these two types of mutations were comparatively investigated in this study. METHODS: One hundred and sixty-five sera with positive anti-HBe and HBV DNA were collected from different patients. Mutations of G1896A and A1762T/G1764A among these serum samples were detected using competitively differentiated PCR. HBV DNA was demonstrated using real-time quantitative PCR. RESULTS: G1896A and/or A1762T/G1764A mutations were detected in 89.1% (147/165) out of patients with detectable HBV DNA in serum after HBeAg-to-anti-HBe seroconversion. The positive rate of G1896A variants was significantly higher than that of A1762T/G1764A mutations (77.6% vs 50.3%, chi2 = 26.61, P<0.01). The coexistence positive rate of these two types of mutations was 38.8% (64/165). Coexistence mutations were found in 77.1% (64/83) out of sera with A1762T/G1764A mutations, and in 50.0% (64/128) out of sera with G1896A mutation. Compared with variants with G1896A mutation only, the coexistence mutations were predominant in patients with high level of serum HBV DNA, and related to higher total bilirubin, lower serum albumin and progressive liver diseases. CONCLUSION: The coexistence of G1896A mutation and A1762T/G1764A mutations is very common, and responsible for the major cases with high level of HBV DNA in serum and progressive liver diseases after HBeAg-to-anti-HBe seroconversion. This coexistence mutation variant may have higher pathogenicity and replication ability.

Adult↗
PubMed2000

Accurate and rapid "multiplex heteroduplexing" method for genotyping key enzymes involved in folate/homocysteine metabolism.

BACKGROUND: Hyperhomocysteinemia, which is often associated with low folate status, is an independent risk factor for cardiovascular diseases and several other pathologies. The four most common functional polymorphisms in genes involved in folate/homocysteine metabolism are methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MS) A2756G, and cystathionine beta-synthase (CBS) 844ins68. The pathogenic impact of these variants is under active investigation in many laboratories. However, conventional genotyping methods, mostly using PCR followed by restriction enzyme digestion, often are compromised by partial fragment digestion. There is, therefore, a need to develop more reliable approaches to genotyping the above polymorphisms that may be applied in large-scale studies. METHODS: Sequence-specific heteroduplex generators for each of the MTHFR and MS single nucleotide polymorphisms were generated by site-directed mutagenesis. These were subcloned into a single construct, pHcyHG-1, which could be multiplexed with a simple PCR amplification across the CBS 844ins68 polymorphic site to generate composite genotype-specific banding patterns from individual genomic DNA samples that could be electrophoretically resolved. RESULTS: The "multiplex heteroduplexing" method yielded unambiguous MTHFR, MS, and CBS genotypes in a single-tube reaction that could be analyzed in a single gel run. CONCLUSIONS: This method permits unambiguous genotyping of the four most common functional variants of enzymes involved in folate/homocysteine metabolism. It is rapid, reproducible, and inexpensive, and requires no special preparative or analytic facilities; consequently, it will facilitate large-scale studies of the genetic basis of hyperhomocysteinemia and the many pathologies that have been associated with this phenotype.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMedDate not supplied

Molecular characterization of infectious bronchitis virus isolates foreign to the United States and comparison with United States isolates.

Eleven infectious bronchitis virus (IBV) isolates foreign to the United States were analyzed by using reverse transcriptase (RT)-polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) and S1 glycoprotein gene sequencing. Two of the isolates generated RFLP patterns that resembled the Mass 41 strain. Seven novel RFLP patterns were detected among the other nine foreign IBV isolates. Five of the foreign isolates were further analyzed by S1 glycoprotein gene sequencing in our laboratory. Phylogenetic analysis of S1 glycoprotein-deduced amino acid sequences for 4/91 pathogenic, 4/91 attenuated, and Variant 1 were greater than 90% similar to viruses belonging to the 793/B serogroup and, therefore, are possibly serologically related. Variant 2 was only 81.0% similar to viruses belonging to the European serogroup B, and, therefore, predicting its serotype is difficult. Isolates 98-07484 and 97-8123 were genotypically unique and therefore might be serologically unique. With the RFLP patterns and the deduced S1 amino acid sequence data as a reference, none of the IBV isolates foreign to the United States have been detected in the United States.

Amino Acid Sequence↗
PubMedDate not supplied

Pathogenicity of cell culture-derived and bursa-derived infectious bursal disease viruses in specific-pathogen-free chickens.

That passage of infectious bursal disease virus (IBDV) 30 and 40 times in an established cell line (BGM-70) resulted in loss of pathogenicity has been reported; however, both viruses maintained antigenicity and immunogenicity. That the passaged virus might have lost some ability to replicate in the natural host, resulting in lack of antigenic stimulation and a poor immune response, was speculated. In this study, the pathogenicity and the replication of the serorype 1 variant IN strain were investigated in specific-pathogen-free (SPF) chickens. The original bursa-derived virus was passaged 10 times (low passage [LP]) and 47 times (high passage [HP]) in BGM-70 cells. Two concentrations of the LP virus were used for inoculation of different groups of birds, high titer 1.5 x 10(5) 50% mean embryo infective dose (EID50) and low titer 1.5 x 10(2) EID50. Birds inoculated with the bursa-derived virus had significantly (P < 0.05) small bursas with severe inflammation and necrosis throughout the 21-day experimental period. Bursa and spleen/body weight ratios and bursal lesion scores of the birds inoculated with the LP and HP viruses were not significantly different from those of the uninoculated control group at any time postinoculation (PI). Virus replication in the bursa of Fabricius was investigated by virus isolation in SPF chicken embryos, immune electron microscopy (IEM), immunofluorescence (IF), and antigen-capture enzyme-linked immunosorbent assay (AC-ELISA). The virus was isolated from bursal tissues from birds inoculated with the bursa-derived virus from day 3 (first isolation attempt) through day 10 PI, and the highest virus concentration was detected at 3 days PI. Low virus titer was detected only at 3 days PI in chicken embryos inoculated with the bursal homogenates from birds inoculated with the LP virus at a high dose or the HP virus. No virus was isolated from birds inoculated with the LP virus at a low dose or the uninoculated control group. The virus antigen was also detected in bursal tissues collected from birds inoculated with the bursa-derived virus at 3, 5, and 7 days PI by IEM and AC-ELISA and until day 10 PI by IF. No virus antigen was detected in bursal tissues collected from birds inoculated with the cell culture-adapted viruses by embryo inoculation, IEM, IF, or AC-ELISA. The virus or its RNA was detected in the bursal homogenates up to 21 days PI by reverse transcriptase/polymerase chain reaction. These results indicated that adaptation of IBDV to BGM-70 cell culture resulted in a significant reduction in the ability of the virus to replicate in the bursa of Fabricius, and, consequently, no lesions were detected.

Animals↗
PubMed2004

Can modulation of viral fitness represent a target for anti-HIV-1 strategies?

Prolonged use of anti-retroviral compounds in human immunodeficiency virus type 1 (HIV-1) infection selects for drug-resistant and often mutidrug-resistant viral variants. Drug-resistance mutations may also affect viral fitness. Interestingly, recent research has indicated that some of the unfit drug-resistant variants may be less pathogenic, suggesting that decreased viral fitness is beneficial for the host and may be driven by specific treatments during anti-HIV-1 infection. A second potential antiviral strategy starting with profound inteference with viral fitness aims at forcing viruses towards lethal mutagenesis (the so-called "error catastrophe"). This review summarizes the methods for addressing HIV-1 fitness in vitro and ex vivo, the current understanding of clinical implications of reduced HIV-1 fitness, and the potential use of anti-HIV-1 strategies aiming at modulating viral fitness. Finally, it is emphasized how the peculiar features of HIV-1 quasispecies (displaying two different forms of memory, a replicative and a non-replicative form) may sharply influence the design of future diagnostic methodologies for fitness analysis.

Drug Resistance, Viral↗
PubMed1977

[Surgical wound dehiscence after esophageal anastomosis in radical surgery of cancer of the cardia].

The authors have analysed 64 observations of suture incompetency of esophageal anastomosis after resection for cancer of the gastric cardiac portion. Three pathogenic phases and three variants of the clinical course are distinguished in the development of the complication. The successful treatment of the complication largely depends on its recognition and properly selected method of treatment with relation to a variant of the course, a phase of the process and terms of its diagnosis.

Cardia↗
PubMed1997

[Characterization of isolated adenovirus associated with acute lower respiratory infection in pediatrics].

BACKGROUND: Acute respiratory infection (ARI) are a health care problem as the adenovirus (ADV) has shown to be one of the most frequent viral agents detected in children admitted for mild ARI in the authors medium. METHODS: Over a 7-year period (1988-1994) ADV isolated from patients under the age of 5, admitted for mild ARI in hospitals in the city of Buenos Aires (Argentina). All the strains were isolated in HEp-2 cell cultures from nasopharyngeal aspirates in which the presence of ADV was detected by indirect immunofluorescence with monoclonal antibodies. Antigenic characterization was performed by sero- and genome neutralization with restriction enzymes. RESULTS: The isolates corresponded to the genomic variants of ADV 7i, ADV 7c and to a greater number of ADV 7h. An increase was observed in the quantity of cases in the second half of the year. In the population studied, the most commonly infected were males (67.9%) and patients from 2 months to 1 year in age (89.2%). Sixty-six percent of the cases were severe infections with the length of hospitalization being greater than that of patients normally admitted for mild ARI by other virus and showed a high mortality. CONCLUSIONS: All the above events suggest that the genomic variants detected are highly pathogenic.

Adenoviruses, Human↗
PubMed1992

Molecular and genetic characterization of cytochrome oxidase-negative Aeromonas salmonicida isolated from coho salmon (Oncorhynchus kisutch).

Cytochrome oxidase variants of the bacterial fish pathogen, Aeromonas salmonicida, were characterized for genetic and molecular homology with cytochrome oxidase-positive isolates that typically induce furunculosis in salmonids. Protein and lipopolysaccharide moieties of the cytochrome oxidase-negative variants were similar to their typical counterparts, based on sodium-dodecyl-sulfate polyacrylamide gel electrophoresis. Pathogenicity of aberrant isolates to brook trout (Salvelinus fontinalis) was similar to typical cytochrome oxidase-positive isolates. Colorimetric deoxyribonucleic acid (DNA) hybridization in 96-well microplates yielded homology values greater than 82.5% for typical aberrant A. salmonicida isolates when photobiotinylated DNA for reference A. salmonicida 3.101 was used as a probe. The only variation of these isolates from typical A. salmonicida was a negative cytochrome oxidase reaction.

Aeromonas↗
PubMed2006

Variant antigen gene expression in malaria.

Pathogens of the genus Plasmodium are unicellular parasites that infect a variety of animals, including reptiles, birds and mammals. All Plasmodium species target host erythrocytes and replicate asexually within this niche. In humans, proliferation within erythrocytes causes disease symptoms ranging from asymtomatic infection to severe disease, including mild to severe febrile and respiratory symptoms, profound anaemia and obstruction of blood flow. The most serious form of human malaria is caused by Plasmodium falciparum, a pathogen that is responsible for several million deaths annually throughout the developing world. Malaria parasites succeed in evading the host immune response to establish long-term, persistent infections, thus increasing the efficiency by which they are transmitted to the mosquito vector. The ability to evade the host immune system, in particular the avoidance of antibody-mediated immunity against parasite-encoded surface proteins, is the result of amplification of extensive repertoires of multicopy, hypervariable gene families that encode infected erythrocyte or merozoite surface proteins. Via switching between antigenically diverse genes within these large families, populations of parasites have the capacity for rapid variation in antigenicity and virulence over the course of an infection. Here we review the amplification and generation of antigenic diversity within the Plasmodium variant gene families, as well as discuss the mechanisms underlying their tightly controlled gene expression and antigenic switching.

Animals↗
PubMed1998

Persistence of human herpesvirus 6 according to site and variant: possible greater neurotropism of variant A.

Little is known of the persistence and pathogenicity of human herpesvirus 6 (HHV-6) after primary infection, including the role of strain variant. Over 2 to 5 years, 2,716 children and 149 families were studied. Peripheral blood mononuclear cell (PBMC), saliva, and cerebrospinal fluid (CSF) specimens were examined for HHV-6 DNA and variant. Ninety-nine percent of isolates causing primary infection were HHV-6 variant B (HHV-6B), which predominated in 95%-98% of the variants persisting in PBMC and saliva specimens from children and adults. Of 668 CSF samples, 13% contained HHV-6 DNA; of 77 children examined after primary infection, 61% had HHV-6 DNA detected only in their CSF and 39% had HHV-6 DNA in both CSF and PBMCs. HHV-6 variant A (HHV-6A) was detected significantly (P = .0001) more frequently in CSF than in PBMCs or saliva. In children for whom HHV-6 was identified in both CSF and PBMCs, PBMCs contained only HHV-6B, while CSF contained HHV-6A or HHV-6B, not both. Thus, in patients with dual infection, only HHV-6A persisted in CSF, which suggests that HHV-6A has greater neurotropism. Findings for adults indicate that dual infection occurs; variant persistence is similar to that for children. The frequency of HHV-6A infection increased little with age, thereby indicating that HHV-6A infection remains uncommon into adulthood. This study suggests that HHV-6 variants have different immunobiologic courses and neurotropism.

Adult↗
PubMed2006

Genetic relatedness of a non-motile variant O157 enteropathogenic Escherichia coli (EPEC) strain and E. coli strains belonging to pathogenic related groups.

The study was undertaken to determine the clonal relationship and the genetic diversity among Escherichia coli isolates by comparing a non-motile O157 variant with three O157:H7 EHEC isolates and one O55:H7 enteropathogenic E. coli (EPEC) strain. E. coli strains were characterized by sorbitol phenotype, multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, random amplification polymorphic DNA, and the presence of specific virulence genes (stx, E-hly and LEE genes). Sorbitol fermentation was observed in O157:H- (strain 116I), O55:H7 and O157:H7 (strain GC148) serotypes. stx1 or stx2 and E-hly genes were only detected among O157:H7 isolates. LEE typing revealed specific allele distribution: eaegamma, tirgamma, espAgamma, espBgamma associated with EPEC O55:H7 and EHEC O157:H7 strains (B1/1 and EDL 933), eaealpha, tiralpha, espAalpha, espBalpha related to the 116I O157:H- strain and the GC148 strain presented non-typable LEE sequences. Multilocus enzyme profiles revealed two main clusters associated with specific LEE pathotypes. E. coli strains were discriminated by random amplification of polymorphic DNA-polymerase chain reaction and pulsed-field gel electrophoresis methodologies. The molecular approaches used in this study allowed the determination of the genetic relatedness among E. coli strains as well as the detection of lineage specific group markers.

Animals↗
PubMed2023

H4C5 missense variant leads to a neurodevelopmental phenotype overlapping with Angelman syndrome.

Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly, and facial dysmorphisms. A 4-year-old male with autism, developmental delay, microcephaly, and a happy demeanor underwent evaluation through the Undiagnosed Disease Network. He was clinically suspected to have Angelman syndrome; however, molecular testing was negative. Genome sequencing identified the H4 histone gene variant H4C5 NM_003545.4: c.295T>C, p.Tyr99His, which parental testing confirmed to be de novo. The variant met criteria for a likely pathogenic classification and is one of the seven known disease-causing missense variants in H4C5. A comparison of our proband's findings to the initial description of the H4-associated neurodevelopmental syndrome demonstrates that his phenotype closely matches the spectrum of those reported among the 29 affected individuals. As such, this report corroborates the delineation of neurodevelopmental syndrome caused by de novo missense H4 gene variants. Moreover, it suggests that cases of clinically suspected Angelman syndrome without molecular confirmation should undergo exome or genome sequencing, as novel neurodevelopmental syndromes with phenotypes overlapping with Angelman continue to be discovered.

Male↗
PubMed2001

The antiviral resistance and replication of cidofovir-resistant adenovirus variants in the New Zealand White rabbit ocular model.

PURPOSE: To determine the antiviral resistance of three cidofovir (CDV)-resistant variants of adenovirus type 5 (Ad5) and their ability to replicate in the New Zealand White rabbit ocular model. METHODS: Rabbits were inoculated topically in both eyes with the CDV-resistant variants R1, R2, and R3, and the Ad5 parental strain. On day 1, rabbits from each virus inoculation were divided into two topical treatment groups: 0.5% CDV and PBS control. Treatment was administered twice daily in both eyes for 7 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Using viral outcome parameters, CDV resistance was determined for each virus by comparing each CDV-treated virus group to its respective PBS control, and altered pathogenesis was assessed by comparing viral replication in the PBS control groups of the Ad5 parent and the three resistant variants. RESULTS: Topical 0.5% CDV treatment demonstrated significant antiviral inhibitory activity in the Ad5 parental group (e.g., reduced total Ad5-positive cultures, reduced daily Ad5-positive cultures on days 5, 9, 11, and 14, and duration of ocular shedding), but had no effect on the three CDV-resistant variants. There were no significant differences in pathogenicity between the Ad5 parent and the CDV-resistant variants. CONCLUSIONS: The Ad5 variants R1, R2, and R3 were resistant to topical treatment with 0.5% cidofovir in the rabbit ocular model. However, the acquisition of CDV resistance did not alter the replication of the three Ad5 CDV variants on the rabbit eye.

Adenoviridae Infections↗
PubMed2004

Intra-host evolution of human immunodeficiency virus type 1 and viral fitness.

RNA viruses are frequently tolerant to high levels of mutagenesis. In contrast, DNA viruses are less errorprone and coevolve along with their specific hosts over long time periods. Although both strategies have been successful, the "RNA-strategy" (directly linked to the pathogenic potential of these agents) most often generates novelty (new variants, new strains, and even new viral pathogens). For several decades, intra-host virus evolution has been considered to be a speculative field, far from the main issues of clinical virology. This concept is now changed, due to the evidence that RNA virus evolution is intimately linked to failures in viral disease control and prevention. Antiviral strategies using single and fixed elements (i.e. treatments using one antiviral compound, immunizations using a single recombinant protein) have been unable to control highly dynamic quasispecies, such as human immunodeficiency virus type I (HIV-1) and hepatitis C virus (HCV). The development of combinatorial treatments in HIV-1 infection and the recognition that vaccines should be multivalent are important steps in adapting disease control strategies to the complexity of viral populations. The present report summarizes the strategies adopted to address HIV-1 evolution and its phenotypic consequences, including changes in susceptibility to antiviral compounds, viral fitness, and pathogenic potential. In particular, it is highlighted that sequence-function analyses of the intra-host HIV-I evolution, including studies of viral fitness, have opened up new perspectives not only to studying the pathogenic mechanisms and the virus-host relationships, but also to designing new strategies for monitoring antiviral therapies.

AIDS Vaccines↗
PubMed1996

Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239delta3 in adult and infant rhesus monkeys.

Variants of SIV containing a deletion in the nef gene are attenuated in adult macaques, where they provide protection from challenge with pathogenic SIV, but the mechanism of protection remains unknown. One of these attenuated variants carrying deletions in nef, vpr, and NRE (SIVmac239delta3) was recently found to be pathogenic in infant macaques exposed to the virus at birth. We investigated whether inadequate or inappropriate antiviral humoral immune responses could explain why this virus causes disease in infant macaques. Plasma samples from four infants infected with SIVmac251 and five infants and two adults infected with SIVmac239delta3 were evaluated for neutralizing Abs to a laboratory-passaged stock of SIVmac251, an animal challenge stock of SIVmac239/nef-open, and a stock of SIVmac239delta3 to which animals were exposed. Plasma samples were evaluated further for complement-mediated Ab-dependent enhancement (C'-ADE) of SIVmac239/nef-open in vitro. High-titer neutralizing Abs to SIVmac251 were detected in plasma samples from adults and most infants within 3 to 5 wk of infection with either virus. Neutralizing Abs to SIVmac239/nef-open and SIVmac239delta3 developed more slowly, being undetectable before 23 to 63 wk of infection. Timing, magnitude, and breadth of neutralizing Ab responses did not correlate with progression to disease or lack thereof and gave no indication of an impaired humoral immune response in infants. Furthermore, C'-ADE was detected equally in plasma samples from adults and infants. The results indicate that infection with SIVmac239delta3 causes disease in infant macaques despite their mounting of antiviral humoral immune responses comparable to those of adults.

Age Factors↗
PubMed2006

Is this a variant of Lemierre's syndrome?

Lemierre's syndrome is an oropharyngeal infection leading to secondary septic thrombophlebitis of the internal jugular vein (IJV). It is classically anaerobic in origin and Fusobacterium necrophorum is the commonest pathogen. We report an unusual variant of this condition in a 68-year-man with uncontrolled diabetes mellitus who presented with extensive cellulitis of the left neck. No primary oropharyngeal sepsis was detected. Neck radiographs revealed soft tissue gas and computed tomography confirmed neck space infection with gas formation and complete thrombosis of the left IJV. Klebsiella pneumoniae was isolated from the fluid, tissue and blood samples. Repeated debridement was required until complete healing. Computed tomography of the neck at six months showed resolution of infection, although the vein remained thrombosed. Although the radiological features resemble Lemierre's syndrome, this case differs from it in the absence of oropharyngeal sepsis and presence of background diabetes mellitus. The isolation of Klebsiella pneumoniae as a cause has not been previously described.

Aged↗
PubMed2004

Immunological detection and cytotoxic properties of toxins from toxin A-positive, toxin B-positive Clostridium difficile variants.

Clostridium difficile is a major nosocomial pathogen and a causative agent of antibiotic-associated diarrhoea and pseudomembranous colitis. PCR analysis of the toxin A and B genes of this bacterium has revealed 20 variant types (toxinotypes I-XX), many of which can cause human disease. Strains comprising the 15 toxin A-positive, toxin B-positive toxinotypes are not usually differentiated from non-variant strains by routine laboratories that do not utilize PCR tests. Consequently, the toxins from these variant strains have not been investigated thoroughly. The present studies revealed that toxin A-positive (A+B+) strains representing 12 variant toxinotypes all express considerably lower levels of toxin A and are less cytotoxic in vitro than non-variant strain VPI 10463. Truncated forms of toxin A were detected by immunoblotting in toxinotype VI and VII strains and these toxins were differentiated from each other and from toxin A of the non-variant strain. A further novel finding was the ability of toxin A-positive (A+B+) strains of toxinotypes IX, XIV and XV to exhibit an alternative Clostridium sordellii-like cytopathic effect on Vero cells, characterized by marked cell clumping. A rapid and simple method for toxin A removal from culture filtrates was developed. This enabled confirmation that the abnormal cytotoxicity observed for these strains is due to an altered toxin B, as has been found in toxin A-negative (A-B+) strains. These findings indicate the potential for differentiation of certain toxin A-positive (A+B+) toxinotypes without the need for PCR techniques.

Animals↗