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Multiple herpesviruses have been recently found to encode viral circular RNAs. Like cellular circular RNAs, these RNAs lack poly-A tails and their 5′ and 3′ ends have been joined, which confers protection from RNA exonucleases. We examined the expression patterns of circular RNAs from Kaposi’s sarcoma herpesvirus (KSHV) in various environments. We performed deep sequencing of circRNA-enriched total RNA from a KSHV-positive patient lymph node for comparison with previous circRNA-Seq results. We found that circvIRF4 is highly expressed in the KSHV-positive patient sample relative to both B cell lines and de novo infected primary vascular and lymphatic endothelial cells (LECs). Overall, this patient sample showed a viral circRNA expression pattern more similar to the pattern from B cell lines, but we also discovered new back-spliced junctions and additional viral circular RNAs in this patient sample. We validated some of these back-spliced junctions as circular RNAs with standard assays. Differential expression patterns of circular RNAs in different cell types led us to investigate what cellular factors might be influencing the ratio of viral linear mRNAs to circular RNAs. We found that repression of certain RNA-binding proteins shifted the balance between viral linear mRNAs and circular RNAs. Taken together, examining viral circular RNA expression patterns may become useful tools for discovering their functions, the regulators of their expression, and determining the stage and cell types of infection in humans.

Background Despite advances in diagnostic methods and antibiotic therapy, community-acquired pneumonia (CAP) is still a major cause of morbidity and mortality worldwide. Risk of CAP has been attributed to pathogen virulence, host susceptibility and epidemiologic factors. A significant number of patients with CAP develop severe complications, such as sepsis, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS) and less fatal conditions (pleuritis, empyema) and syndromes (acute respiratory failure (ARF)). The variable clinical presentation of CAP suggests a genetic predisposition. Materials and methods This study was conducted to establish the possible contribution of functional gene polymorphisms in the oxidative stress related genes to the development of community-acquired pneumonia (CAP) complications. CAP subjects (n = 350) were genotyped for 16 polymorphic variants in the genes of xenobiotics detoxification CYP1A1, AhR, GSTM1, GSTT1, ABCB1, redox-status SOD2, CAT, GCLC, and vascular homeostasis ACE, AGT, AGTR1, NOS3, MTHFR, VEGFa. Results The multilocus model which included six or more risk alleles in the CYP1A1, GCLC, AGT and AGTR1 genes was associated with pleuritis, empyema, acute respiratory distress syndrome (ARDS), all pulmonary complications together and acute respiratory failure. Genetically mediated correlation between clinical conditions in CAP patients is shown in Table 1. In silico analysis with Set Distiller mode identified N-acetylcysteine (P = 1.08E-08) and oxygen (P = 1.92E-06) as the best descriptors for the considered gene set. Acute infections of the airways are associated with oxidative stress, which enhances viscosity of bronchial mucus, reduces the mucociliary clearance rate and expedites lung disease aggravation and progression. N-acetylcysteine is a wellknown mucolytic and antioxidant drug, an indirect precursor of glutathione. Conclusions The results of the study indicate that pneumonia aggravation up to destructive intrapulmonary complications and ARDS is mediated by polymorphisms in oxidative stress-related genes. P3 A retrospective study evaluating the efficacy of identification and management of sepsis at a Western Cape Province district level hospital internal medicine department, in comparison to the guidelines stipulated in the Surviving Sepsis Campaign 2012

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