30 research outputs found
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness
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Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis
Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie
Type I IRGs are slightly enriched before onset of symptoms, but some IRGs show no change.
<p>(A) Superarray analysis by qPCR was performed on 70 timepoints from 52 subjects to assess the time course of gene expression. Average fold changes for three groups of genes (Type I IRG, Type II IRG, and Cell Cycle as defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085422#pone.0085422.s001" target="_blank">Figure S1</a>) were determined for samples collected within the indicated time blocks. Fold changes are compared with healthy baselines. Error bars show the standard deviation. All three gene groupings had a p-value<0.05 when evaluated by ANOVA. (−20 days to −1 days N = 11; 0 days to 3 days N = 12; 4 days to 7 days N = 17; 8 days to 10 days N = 16). (B) The table shows the average fold change for nine select type I IRGs derived from microarray analysis for SLE, YFV, Flu, HRV, RSV, DENV, Poly IC, and EBV. (C) Heatmaps showing fold change as determined by qPCR for <i>OAS1</i>, <i>MX1</i>, and <i>HERC5</i> at multiple timepoints in EBV infection (top panel) or in other situations (bottom panel).</p