RNA virus genomes contain cis-acting sequence and structural elements that participate in viral replication. We previously identified a bulged stem-loop secondary structure at the upstream end of the 3 untranslated region (3 UTR) of the genome of the coronavirus mouse hepatitis virus (MHV). This element, beginning immediately downstream of the nucleocapsid gene stop codon, was shown to be essential for virus replication. Other investigators discovered an adjacent downstream pseudoknot in the 3 UTR of the closely related bovine coronavirus (BCoV). This pseudoknot was also shown to be essential for replication, and it has a conserved counterpart in every group 1 and group 2 coronavirus. In MHV and BCoV, the bulged stem-loop and pseudoknot are, in part, mutually exclusive, because of the overlap of the last segment of the stem-loop and stem 1 of the pseudoknot. This led us to hypothesize that they form a molecular switch, possibly regulating a transition occurring during viral RNA synthesis. We have now performed an extensive genetic analysis of the two components of this proposed switch. Our results define essential and nonessential components of these structures and establish the limits to which essential parts of each element can be destabilized prior to loss of function. Most notably, we have confirmed the interrelationship of the two putative switch elements. Additionally, we have identified a pseudoknot loop insertion mutation that appears to point to a genetic interaction between the pseudoknot and a distant region of the genome.Embedded in the genomes of RNA viruses are cis-acting sequence and structural elements that participate in replication, transcription, translation, and packaging. Some of these signals are thought to facilitate the selective interactions of viral RNAs with the machinery of RNA synthesis, while others enable or modulate events that occur during viral protein synthesis or assembly. The coronaviruses and arteriviruses, members of the order Nidovirales, are positive-strand RNA viruses with very large genomes (13 to 15 kb for arteriviruses, 27 to 31 kb for coronaviruses). In addition to the production of progeny genome copies, nidovirus replication entails the synthesis of a 3Ј nested set of subgenomic (sg) mRNAs (15). Each sgRNA contains a 5Ј leader segment connected to a body segment that is identical to the 3Ј end of the genome, starting at a given point preceding one of the downstream open reading frames. Accumulating evidence, particularly from landmark studies using a full-length infectious cDNA of equine arterivirus, supports a model in which the discontinuous step in sgRNA formation occurs during negative-strand RNA synthesis (1,28,31,35). Thus, for nidoviruses, the earliest steps of both genome replication and sgRNA transcription initiate at the 3Ј end of the genome; therefore, it is reasonable to expect that at least part of the regulation of these processes is implicit in the sequence and structure of the 3Ј untranslated region (3Ј UTR). Indeed, studies of defective interfering...

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Case: A 50-year-old woman with a prior right carotid aneurysm repair presented for chest pain. An evaluation 13 years ago showed a normal echo and cardiac catheterization. Four years prior, an echo showed an enlarged left ventricle with ejection fraction 57% and mid-anterolateral and inferolateral wall hypokinesis. Coronary angiography showed diffuse aneurysms of all coronary arteries with a proximal stenosis of the LAD, followed by a giant coronary aneurysm (Figure 1). CT angiography revealed bilateral intercostal artery aneurysms and a mildly ectatic aorta. She underwent bypass of the LAD with the LIMA. Aortic biopsy revealed no aortitis and prior carotid aneurysm pathology showed plasmalymphocytic inflammation; labs showed hypereosinophilia and elevated inflammatory markers with other negative immunologic work-up. She was diagnosed with hypereosinophilic vasculitis without evidence of granulomatosis and started on immunosuppressants.Due to symptoms, she underwent coronary angiography. Her LAD was occluded ostially with distal flow via a patent LIMA (Figure 2). There was progression of her aneurysmal disease at her proximal right coronary artery. No intervention was recommended. Instead, to improve control of her vasculitis, a Janus kinase inhibitor will be started. Discussion: Hypereosinophilic vasculitis, a variant of eosinophilic granulomatosis with polyangiitis, affects small- and medium-sized arteries and is challenging to diagnose. This case highlights a rare cardiac complication that can occur with this condition. Cardiac involvement often manifests as heart failure, pericarditis, valvular insufficiency, or rarely, coronary aneurysms.

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