Recovery and sequence analysis of hepatitis a virus from springwater implicated in an outbreak of acute viral hepatitis.
Ontology highlight
ABSTRACT:
SUBMITTER: Tallon LA
PROVIDER: S-EPMC2565947 | biostudies-literature | 2008 Oct
REPOSITORIES: biostudies-literature
Publications
Recovery and sequence analysis of hepatitis a virus from springwater implicated in an outbreak of acute viral hepatitis.
Tallon Lindsay A LA Love David C DC Moore Zack S ZS Sobsey Mark D MD
Applied and environmental microbiology 20080815 19
An outbreak of acute hepatitis A virus in North Carolina was linked to drinking water from a contaminated shallow spring by phylogenetic analysis of hepatitis A virus (HAV) genomic sequences. Detection of HAV and fecal indicators in the water provided useful and timely information to assist with public health prevention and control measures. ...[more]
Similar Datasets
Project description:CD8(+)-T-cell responses play an important role in the containment and clearance of hepatitis C virus (HCV) infection, and an association between viral persistence and development of viral escape mutations has been postulated. While escape from CD8+ -T-cell responses has been identified as a major driving force for the evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), a broader characterization of this relationship is needed in HCV infection. To determine the extent, kinetics, and driving forces of HCV sequence evolution, we sequenced the entire HCV genome longitudinally in four subjects monitored for up to 30 months after acute infection. For two subjects the transmission sources were also available. Of 53 total non-envelope amino acid substitutions detected, a majority represented forward mutations away from the consensus sequence. In contrast to studies in HIV and SIV, however, only 11% of these were associated with detectable CD8+ T-cell responses. Interestingly, 19% of non-envelope mutations represented changes toward the consensus sequence, suggesting reversion in the absence of immune pressure upon transmission. Notably, the rate of evolution of forward and reverse mutations correlated with the conservation of each residue, which is indicative of structural constraints influencing the kinetics of viral evolution. Finally, the rate of sequence evolution was observed to decline over the course of infection, possibly reflective of diminishing selection pressure by dysfunctional CD8+ T cells. Taken together, these data provide insight into the extent to which HCV is capable of evading early CD8+ T-cell responses and support the hypothesis that dysfunction of CD8+ T cells may be associated with failure to resolve HCV infections.
| S-EPMC2168804 | biostudies-literature
Project description:Background and Aims: Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses our goal was to analyze gene expression in DC from patients during acute HCV infection. Methods: By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from those who become chronically infected (ANR), as well as in HCV chronically infected patients (CHR) and healthy seronegative individuals (CTRL). Results: For pDC, a high number of upregulated genes related to different functions and processes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Differences between AR and ANR were also observed when comparing their DC with those from CHR patients and CTRL individuals. Most differences corresponded to metabolism-associated genes, with upregulation in AR patients of genes belonging to pathways associated with DC activation and cytokine responses. Conclusion: Our results show that upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection. Gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from those who become chronically infected (ANR), as well as in HCV chronically infected patients (CHR) and healthy seronegative individuals (CTRL)
2016-07-29 | E-GEOD-65123 | biostudies-arrayexpress
Project description:Background and Aims: Viral clearance during acute hepatitis C virus (HCV) infection is associated with the induction of potent antiviral T-cell responses. Since dendritic cells (DC) are essential in the activation of primary T-cell responses our goal was to analyze gene expression in DC from patients during acute HCV infection. Methods: By using microarrays, gene expression was compared in resting and activated peripheral blood plasmacytoid (pDC) and myeloid (mDC) DC from acute HCV resolving patients (AR) and from those who become chronically infected (ANR), as well as in HCV chronically infected patients (CHR) and healthy seronegative individuals (CTRL). Results: For pDC, a high number of upregulated genes related to different functions and processes was found in AR patients, irrespective of DC stimulation. However, for mDC, most evident differences were detected after DC stimulation, again corresponding to upregulated genes in AR patients. Differences between AR and ANR were also observed when comparing their DC with those from CHR patients and CTRL individuals. Most differences corresponded to metabolism-associated genes, with upregulation in AR patients of genes belonging to pathways associated with DC activation and cytokine responses. Conclusion: Our results show that upregulation of relevant genes in DC during acute HCV infection may determine viral clearance, suggesting that dysfunctional DC may be responsible for the lack of efficient T-cell responses which lead to chronic HCV infection.
2016-07-29 | GSE65123 | GEO
Project description:Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required.
| S-EPMC4726789 | biostudies-literature
Project description:BackgroundIn Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined.MethodsReported AVH incidence data from 1971 to 2005 and AVH-associated mortality data from 1981 to 1995 were examined. Serologic markers for infection with hepatitis viruses A, B, D, and E were determined from a sample of hospitalized patients with AVH from an epidemic period (1987) and from a sample of pregnant women with AVH from a non-epidemic period (1992).ResultsTwo multi-year AVH outbreaks were identified: one during 1975-1976, and one during 1985-1987. During 1985-1987, AVH-associated MRs were 12.3-17.8 per 100,000 for the general population. Highest AVH-associated MRs occurred among children in the first 3 years of life (40-190 per 100,000) and among women aged 20-29 (15-21 per 100,000). During 1988-1995 when reported AVH morbidity was much lower in the general population, AVH-associated MRs were markedly lower among these same age groups. In 1988, AVH-associated MRs were higher in rural (21 per 100,000) than in urban (8 per 100,000) populations (RR 2.6; 95% CI 1.16-5.93; p < 0.05). Serologic evidence of acute HEV infection was found in 280 of 396 (71%) patients with AVH in 1987 and 12 of 99 (12%) pregnant patients with AVH in 1992.ConclusionIn the absence of the availability of confirmatory testing, inferences regarding probable hepatitis epidemic etiologies can sometimes be made using surveillance data, comparing AVH incidence with AVH-associated mortality with an eye to population-based viral hepatitis control measures. Data presented here implicate HEV as the probable etiology of high mortality observed in pregnant women and in children less than 3 years of age in Uzbekistan during 1985-1987. High mortality among pregnant women but not among children less than 3 years has been observed in previous descriptions of epidemic hepatitis E. The high mortality among younger children observed in an AVH outbreak associated with hepatitis E merits corroboration in future outbreaks.
| S-EPMC2671511 | biostudies-literature
Project description:Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.
| S-EPMC3164670 | biostudies-literature
Project description:Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the determinants of spontaneous resolution versus chronicity remain incompletely understood. In particular, because of the retrospective nature and unknown source of infection in most human studies, direct evidence for emergence of escape mutations in immunodominant major histocompatibility complex class I-restricted epitopes leading to immune evasion is extremely limited. In two patients infected accidentally with an identical HCV strain but who developed divergent outcomes, the total lack of HCV-specific CD4+ T cells in conjunction with vigorous CD8+ T cells that targeted a single epitope in one patient was associated with mutational escape and viral persistence. Statistical evidence for positive Darwinian selective pressure against an immunodominant epitope is presented. Wild-type cytotoxic T lymphocytes persisted even after the cognate antigen was no longer present.
| S-EPMC2213272 | biostudies-literature
Project description:Chimeric urokinase type plasminogen activator (uPA)/severely severe combined immunodeficiency (SCID) mice reconstituted with humanized livers are useful for studying hepatitis B virus (HBV) infection in the absence of an adaptive immune response. However, the detailed characterization of HBV infection kinetics necessary to enable in-depth mechanistic studies in this in vivo HBV infection model is lacking. To characterize HBV kinetics post-inoculation (p.i.) to steady state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured from 1 minute to 63 days p.i. Total intrahepatic HBV DNA, HBV covalently closed circular DNA (cccDNA), and HBV RNA was measured in a subset of mice at 2, 4, 6, 10, and 13 weeks p.i. HBV half-life (t1/2 ) was estimated using a linear mixed-effects model. During the first 6 hours p.i., serum HBV declined in repopulated uPA/SCID mice with a t1/2 = 62 minutes (95% confidence interval [CI] = 59-67). Thereafter, viral decline slowed followed by a 2-day lower plateau. Subsequent viral amplification was multiphasic with an initial mean doubling time of t2 = 8 ± 3 hours followed by an interim plateau before prolonged amplification (t2 = 2 ± 0.5 days) to a final HBV steady state of 9.3 ± 0.3 log copies (cps)/mL. Serum HBV and intrahepatic HBV DNA were positively correlated (R2 = 0.98). CONCLUSION:HBV infection in uPA/SCID chimeric mice is highly dynamic despite the absence of an adaptive immune response. Serum HBV t1/2 in humanized uPA/SCID mice was estimated to be ?1 hour regardless of inoculum size. The HBV acute infection kinetics presented here is an important step in characterizing this experimental model system so that it can be effectively used to elucidate the dynamics of the HBV life cycle and thus possibly reveal effective antiviral drug targets. (Hepatology 2018).
| S-EPMC6097938 | biostudies-literature
Project description:In contrast to a detailed understanding of antiviral cellular immune responses, the impact of neutralizing antibodies for the resolution of acute hepatitis C is poorly defined. The analysis of neutralizing responses has been hampered by the fact that patient cohorts as well as hepatitis C virus (HCV) strains are usually heterogeneous, and that clinical data from acute-phase and long-term follow-up after infection are not readily available. Using an infectious retroviral HCV pseudoparticle model system, we studied a cohort of women accidentally exposed to the same HCV strain of known sequence. In this single-source outbreak of hepatitis C, viral clearance was associated with a rapid induction of neutralizing antibodies in the early phase of infection. Neutralizing antibodies decreased or disappeared after recovery from HCV infection. In contrast, chronic HCV infection was characterized by absent or low-titer neutralizing antibodies in the early phase of infection and the persistence of infection despite the induction of cross-neutralizing antibodies in the late phase of infection. These data suggest that rapid induction of neutralizing antibodies during the early phase of infection may contribute to control of HCV infection. This finding may have important implications for understanding the pathogenesis of HCV infection and for the development of novel preventive and therapeutic antiviral strategies.
| S-EPMC1851610 | biostudies-literature
Project description:Computer-assisted technologies of the genomic structure, biological function, and evolution of viruses remain a largely neglected area of research. The attention of bioinformaticians to this challenging field is currently unsatisfying in respect to its medical and biological importance. The power of new genome sequencing technologies, associated with new tools to handle "big data", provides unprecedented opportunities to address fundamental questions in virology. Here, we present an overview of the current technologies, challenges, and advantages of Next-Generation Sequencing (NGS) in relation to the field of virology. We present how viral sequences can be detected de novo out of current short-read NGS data. Furthermore, we discuss the challenges and applications of viral quasispecies and how secondary structures, commonly shaped by RNA viruses, can be computationally predicted. The phylogenetic analysis of viruses, as another ubiquitous field in virology, forms an essential element of describing viral epidemics and challenges current algorithms. Recently, the first specialized virus-bioinformatic organizations have been established. We need to bring together virologists and bioinformaticians and provide a platform for the implementation of interdisciplinary collaborative projects at local and international scales. Above all, there is an urgent need for dedicated software tools to tackle various challenges in virology.
| S-EPMC7172532 | biostudies-literature