Dominance of highly divergent feline leukemia virus A progeny variants in a cat with recurrent viremia and fatal lymphoma

ABSTRACT: BACKGROUND: In a cat that had ostensibly recovered from feline leukemia virus (FeLV) infection, we observed the reappearance of the virus and the development of fatal lymphoma 8.5 years after the initial experimental exposure to FeLV-A/Glasgow-1. The goals of the present study were to investigate this FeLV reoccurrence and molecularly characterize the progeny viruses. RESULTS: The FeLV reoccurrence was detected by the presence of FeLV antigen and RNA in the blood and saliva. The cat was feline immunodeficiency virus positive and showed CD4+ T-cell depletion, severe leukopenia, anemia and a multicentric monoclonal B-cell lymphoma. FeLV-A, but not -B or -C, was detectable. Sequencing of the envelope gene revealed three FeLV variants that were highly divergent from the virus that was originally inoculated (89-91% identity to FeLV-A/Glasgow-1). In the long terminal repeat 31 point mutations, some previously described in cats with lymphomas, were detected. The FeLV variant tissue provirus and viral RNA loads were significantly higher than the FeLV-A/Glasgow-1 loads. Moreover, the variant loads were significantly higher in lymphoma positive compared to lymphoma negative tissues. An increase in the variant provirus blood load was observed at the time of FeLV reoccurrence. CONCLUSIONS: Our results demonstrate that ostensibly recovered FeLV provirus-positive cats may act as a source of infection following FeLV reactivation. The virus variants that had largely replaced the inoculation strain had unusually heavily mutated envelopes. The mutations may have led to increased viral fitness and/or changed the mutagenic characteristics of the virus

Identification and Functional Characterization of N-Terminally Acetylated Proteins in Drosophila melanogaster

A new study reveals a functional rule for N-terminal acetylation in higher eukaryotes called the (X)PX rule and describes a generic method that prevents this modification to allow the study of N-terminal acetylation in any given protein

Current concepts relating coronary flow, myocardial perfusion and metabolism in left bundle branch block and cardiac resynchronisation therapy

Cardiac resynchronisation therapy (CRT) improves mortality and symptoms in heart failure patients with electromechanically dyssynchronous ventricles. There is a 50% non-response rate and reproducible biomarkers to predict non-response have not been forthcoming. Therefore, there has been increasing interest in the pathophysiological effects of dyssynchrony particularly focusing on coronary flow, myocardial perfusion and metabolism. Studies suggest that dyssynchronous electrical activation effects coronary flow throughout the coronary vasculature from the epicardial arteries to the microvascular bed and that these changes can be corrected by CRT. The effect of both electrical and mechanical dyssynchrony on myocardial perfusion is unclear with some studies suggesting there is a reduction in septal perfusion whilst others propose that there is an increase in lateral perfusion. Better understanding of these effects offers the possibility for better prediction of non-response. CRT appears to improve homogeneity in myocardial perfusion where heterogeneity is described in the initial substrate. Novel approaches to the identification of non-responders via metabolic phenotyping both invasively and non-invasively have been encouraging. There remains a need for further research to clarify the interaction of coronary flow with perfusion and metabolism in patients who undergo CRT.</p

Delayed Trans-Septal Activation Results in Comparable Hemodynamic Effect of Left Ventricular and Biventricular Endocardial Pacing Insights From Electroanatomical Mapping

Background We sought to compare left ventricular (LVepi) and biventricular epicardial pacing (BIVepi) with LV (LVendo) and BIV endocardial pacing (BIVendo) in patients with chronic heart failure with an emphasis on the underlying electrophysiological mechanisms and hemodynamic effects. Methods and Results Ten patients with chronically implanted cardiac resynchronization devices underwent temporary LVendo and BIVendo pacing with an LV endocardial roving catheter. A pressure wire and noncontact mapping array were placed to the LV cavity to measure LVdP/dt(max) and perform electroanatomical mapping. At the optimal endocardial position, the acute hemodynamic response (AHR) was superior to epicardial stimulation, the AHR to BIVendo pacing and LVendo pacing being comparable (2115% versus 22 +/- 17%; P=NS). During intrinsic conduction, QRS duration was 185 +/- 30 ms, endocardial LV total activation time 92 +/- 27 ms, and trans-septal activation time 60 +/- 21 ms. With LVendo pacing, QRS duration (187 +/- 29 ms; P=NS) and endocardial LV total activation time (91 +/- 23 ms; P=NS) were comparable with intrinsic conduction. There was no significant difference in endocardial LV total activation time between LVendo and BIVendo pacing (91 +/- 23 versus 85 +/- 15 ms; P=NS). Assessment of isochronal maps identified slow trans-septal conduction with both LVendo and BIVendo pacing resulting in activation of almost the entire LV endocardium prior to septal breakout, thereby limiting any possible fusion with either pacing mode. Conclusions The equivalent AHR to LVendo and BIVendo pacing may be explained by prolonged trans-septal conduction limiting fusion of electrical wavefronts. The optimal AHR was associated with predominantly LV pre-excitation and depolarization. Our results suggest that LV pacing alone may offer a viable endocardial stimulation strategy to achieve cardiac resynchronization