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Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines.

Pulsus alternans is characterized by regular rhythm with beat-to-beat alternation of systolic pressures. Left ventricular alternans is usually found in severe left ventricular dysfunction due to cardiomyopathy, coronary artery disease, systemic hypertension, and aortic stenosis. Right ventricular alternans is usually associated with left ventricular alternans, right ventricular dysfunction, pulmonary embolism, and pulmonary hypertension. Biventricular alternans is rare and associated with severe left ventricular dysfunction and left anterior descending coronary artery disease. The exact mechanism of pulsus alternans has not been clearly delineated, and it has been remained a subject of investigation and conjecture since the nineteenth century. Two fundamental mechanisms have been proposed to explain ventricular alteration. The first, based on the Frank-Starling mechanism, proposes beat-to-beat alteration in end-diastolic volume accounted for the alternating contractile force. The second proposed mechanism which explains the physiology of pulsus alternans involves the abnormal calcium handling by cardiac myocytes. To the best of our knowledge, biventricular alternans in pulmonary embolism has not been previously reported in the medical literature. We present and discuss the mechanisms of pulsus alternans and its clinical implications.