Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that causes neurologic disorders in a wide range of animal species. Although the virus is unclassified, sequence analysis of the 8.9-kb viral genome has shown that it is related to rhabdoviruses and paramyxoviruses. We have mapped subgenomic RNAs of BDV strain He80-1 to the viral genome by determining the precise sequences at their 5' and 3' termini. This analysis showed that the genome contains three transcription initiation sites and four termination sites. A 14to 16-nucleotide semiconserved sequence was present at the gene start sites and partially copied into the subgenomic RNAs. The termination sites contained a U-rich motif reminiscent of termination signals in rhabdoviruses and paramyxoviruses. In contrast to the genomes of other nonsegmented, negative-strand RNA viruses, the BDV genome lacked the typical configuration of termination signal, intergenic region, and initiation signal at the gene boundaries. Instead, transcription units and transcription signals frequently overlapped. These differences have implications for our understanding of the control of viral transcription and may relate to the low-level replication and persistence of BDV.

Introduction: The left (LV) and right (RV) ventricles are intrinsically linked directly via shared myofiber and an interventricular septum and indirectly via a closed loop hemodynamic circuit [1], a phenomenon known as ventricular interdependence. While this interdependence has been investigated for over a century [1], the individual contributions of these elements require further investigation and quantification, particularly in heart failure (HF). To address this, we performed in silico experiments that quantify the influence of specific contributors individually to elucidate the effects of LV diastolic dysfunction (DD) and systolic dysfunction (SD) on RV function and vice versa. We hypothesize that our simulations will capture interventricular interactions in HF and RV compensation in LV dysfunction. Materials and Methods: We developed a 6-compartment cardiovascular model that includes a 2-compartment biventricular heart model [2] encapsulated in a simple extensible pericardium [3] and a 4-compartment electrical circuit analog-based circulation model. The ventricles are based on the TriSeg model [2], which approximates the RV and LV free walls and septum as semispherical, thick-walled segments. Active and passive cardiac myofiber mechanics, geometry, and mechanical ventricular interdependence are used to calculate biventricular pressures and volumes. We use nominally healthy values for a 70 kg person for all model parameters. To simulate SD, we reduce active contractile function in the myofiber mechanics model, and for DD, we increase passive myofiber stiffness. Systolic and diastolic function are assessed by the end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR), respectively, over a range of filling volumes. Results: Acute LV SD affects neither RV systolic function nor RV diastolic function. Similarly, acute LV DD affects neither RV systolic function nor RV diastolic function. In contrast, both RV SD and RV DD impair LV filling and cause moderate LV DD with a maintained LV EF. Particularly in RV SD, the slope of the LV EDPVR is increased compared to the healthy case, suggesting LV stiffening. Note, this apparent LV stiffening is not due to either wall thickening or changes in LV passive mechanics but instead due to ventricular interactions and septal bowing. In addition, with increasing LV dysfunction the cardiac power (area of the pressure-volume loop) decreased while the RV cardiac power increased, suggesting RV compensation to maintain a healthy cardiac output. Conclusions: We observed that three dysfunction simulations (LV DD, RV SD, and RV DD) exhibit phenotypes seen in HFpEF (LV DD and EF > 50%), suggesting multiple modes of HF in HFpEF, which is consistent with and may help explain the clinical heterogeneity of HFpEF. With more refined and specific diagnostic categories of HFpEF, more targeted treatments can be developed, which will likely improv outcomes in this disease state. NIH R01HL154624 (NCC and DAB), NIH T32HL116270 (SMK), and NIH T32HL00785322 (EBR) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Treatment of renal anemia with recombinant human erythropoietin (rEPO) frequently raises arterial blood pressure. The objective of this study was to determine whether this is a direct effect of rEPO or a consequence of the expansion of erythrocyte mass. Twenty-three chronic hemodialysis patients receiving maintenance rEPO therapy who had uncontrolled anemia due to iron deficiency were studied. It was anticipated that repletion of iron stores with iv iron dextran would restore rEPO responsiveness, leading to a gradual rise in hematocrit to the target values (0.30 to 0.33). The effect of the increase in hematocrit on arterial blood pressure could then be dissected from the direct effect of rEPO in patients receiving constant doses of rEPO throughout the study period. To this end, arterial blood pressure, iron indices, hematocrit, and measures of fluid balance were monitored at baseline and for a 10-wk period after iron repletion. In eight patients, the hematocrit transiently rose above 0.33, triggering a reduction in rEPO dosage. In the remaining 15 patients, rEPO dosage was held constant during the study period. In this subgroup, repletion of iron stores led to a rise in hematocrit from 0.25 +/- 0.04 to 0.32 +/- 0.04 (P < 0.001) within 4 wk. Despite the significant rise in hematocrit, both systolic and diastolic blood pressure values remained virtually unchanged. Likewise, body weight and interdialytic fluid gain were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)