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Molecular evolution of hepatitis B virus over 25 years.

ABSTRACT: Determining the longitudinal molecular evolution of hepatitis B virus (HBV) is difficult due to HBV's genomic complexity and the need to study paired samples collected over long periods of time. In this study, serial samples were collected from eight hepatitis B virus e antigen-negative asymptomatic carriers of HBV genotype B in 1979 and 2004, thus providing a 25-year period to document the long-term molecular evolution of HBV. The rate, nature, and distribution of mutations that emerged over 25 years were determined by phylogenetic and linear regression analysis of full-length HBV genome sequences. Nucleotide hypervariability was observed within the polymerase and pre-S/S overlap region and within the core gene. The calculated mean number of nucleotide substitutions/site/year (7.9 x 10(-5)) was slightly higher than published estimates (1.5 x 10(-5) to 5 x 10(-5)). Nucleotide changes in the quasispecies population did not significantly alter the molecular evolutionary rate, based on linear regression analysis of evolutionary distances among serial clone pre-S region sequences. Therefore, the directly amplified or dominant sequence was sufficient to estimate the putative molecular evolutionary rate for these long-term serial samples. On average, the ratio of synonymous (dS) to nonsynonymous (dN) substitutions was highest for the polymerase-coding region and lowest for the core-coding region. The low dS/dN ratios observed within the core suggest that selection occurs within this gene region, possibly as an immune evasion strategy. The results of this study suggest that HBV sequence divergence may occur more rapidly than previously estimated, in a host immune phase-dependent manner.

SUBMITTER: Osiowy C

PROVIDER: S-EPMC1641782 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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Molecular evolution of hepatitis B virus over 25 years.

Osiowy Carla C Giles Elizabeth E Tanaka Yasuhito Y Mizokami Masashi M Minuk Gerald Y GY

Journal of virology 20061101 21

Determining the longitudinal molecular evolution of hepatitis B virus (HBV) is difficult due to HBV's genomic complexity and the need to study paired samples collected over long periods of time. In this study, serial samples were collected from eight hepatitis B virus e antigen-negative asymptomatic carriers of HBV genotype B in 1979 and 2004, thus providing a 25-year period to document the long-term molecular evolution of HBV. The rate, nature, and distribution of mutations that emerged over 25 ...[more]

PMID: 17041211

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Project description:UnlabelledBluetongue virus serotype 1 (BTV 1) was first isolated in Australia from cattle blood collected in 1979 at Beatrice Hill Farm (BHF), Northern Territory (NT). From long-term surveillance programs (1977 to 2011), 2,487 isolations of 10 BTV serotypes were made. The most frequently isolated serotype was BTV 1 (41%, 1,019) followed by BTV 16 (17.5%, 436) and BTV 20 (14%, 348). In 3 years, no BTVs were isolated, and in 12 years, no BTV 1 was isolated. Seventeen BTV 1 isolates were sequenced and analyzed in comparison with 10 Australian prototype serotypes. BTV 1 showed an episodic pattern of evolutionary change characterized by four distinct periods. Each period consisted primarily of slow genetic drift which was punctuated from time to time by genetic shifts generated by segment reassortment and the introduction of new genome segments. Evidence was found for coevolution of BTV genome segments. Evolutionary dynamics and selection pressure estimates showed strong temporal and clock-like molecular evolutionary dynamics of six Australian BTV genome segments. Bayesian coalescent estimates of mean substitution rates clustered in the range of 3.5 × 10(-4) to 5.3 × 10(-4) substitutions per site per year. All BTV genome segments evolved under strong purifying (negative) selection, with only three sites identified as under pervasive diversifying (positive) selection. The obligate replication in alternate hosts (insect vector and vertebrate hosts) imposed strong evolutionary constraints. The dominant mechanism generating genetic diversity of BTV 1 at BHF was through the introduction of new viruses and reassortment of genome segments with existing viruses.ImportanceBluetongue virus (BTV) is the causative agent of bluetongue disease in ruminants. It is a disease of concern globally and is transmitted by biting midges (Culicoides species). Analysis of the evolutionary and selection pressures on BTV 1 at a single surveillance site in northern Australia showed strong temporal and clock-like dynamics. Obligate replication in alternate hosts of insect and vertebrate imposed strong evolutionary constraints, with all BTV genome segments evolving under strong purifying (negative) selection. Generation of genetic diversity of BTV 1 in northern Australia is through genome segment reassortment and the introduction of new serotypes.

Project description:This study aimed to review and evaluate our experience in 750 patients, who underwent transhiatal esophagectomy (THE) and analyze our data. Special attention was paid to some strategies, which we developed in the course of time, regarding the postoperative management of these patients and formulation of improved guidelines.This is a retrospective analysis of all THE operations performed between January 1981 until May 2007 in 750 patients: 60 patients (8%) had benign lesions, while 690 (92%) had malignant ones (5.2% of malignancies were located in the upper esophagus, 7.4% in the middle esophagus, 19% in the lower esophagus, and 68.4% at the cardioesophageal junction). THE and esophageal reconstruction were performed at the same operation in all patients. The stomach was our esophageal substitute of first choice with the colon and jejunum being acceptable alternatives in patients with prior gastric surgery and those necessitating synchronous gastrectomy for cancer invasion. A gastric tube was used as an esophageal substitute in 624 patients (83.2%), the whole stomach in 70 (9.4%), the colon in 43 (5.73%), and a jejunal loop in 13 (1.73%).The overall in-hospital mortality rate was 2.93% (22 patients). There was no intraoperative death. Major complications included atelectasis or pneumonia (4.8%), pleural effusion (22.7%), myocardial infarction (0.5%), recurrent laryngeal nerve paralysis (1.33%), and three tracheal lacerations (0.4%). The anastomotic leak rate decreased gradually over time from 29.4% to 11.1% in the last 6 years. The average intraoperative blood loss was 315 ml and 82% of the patients did not receive any blood transfusion. Late functional results were good or excellent in 93%. The average length of hospital stay was 11 days and intensive care unit stay was 2.3 days. The actuarial 5-year survival rate after THE for carcinoma was 21%.THE is a safe and effective method of esophageal resection with low morbidity and mortality rates and good functional results when performed by experienced surgeons. We believe that our strategies concerning the way of dissecting the cervical esophagus, avoidance of performing pyloromyotomy, the delayed removal of the cervical drain and the delayed advance to oral feeding have reduced, noticeably, morbidity and mortality in our series.

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Molecular evolution of hepatitis B virus over 25 years.

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Molecular evolution of hepatitis B virus over 25 years.

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