No abstract

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 U.S. monkeypox cases: the major 2022 outbreak variant, B.1, and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.

No abstract

Sensory perception requires accurate encoding of stimulus information by sensory receptor cells. Here, we identify NCKX4, a potassium – dependent Na+/Ca2+ exchanger, to be necessary for rapid response termination and proper adaptation of vertebrate olfactory sensory neurons (OSNs). Nckx4−/− mouse OSNs display substantially prolonged responses and stronger adaptation. Single – cell electrophysiological analyses demonstrate that the majority of Na+ – dependent Ca2+ exchange in OSNs relevant to sensory transduction is due to NCKX4 and that Nckx4−/− mouse OSNs are deficient in encoding action potentials upon repeated stimulation. Olfactory – specific Nckx4 knockout mice have a reduced ability to locate an odorous source and lower body weights. These results establish the role of NCKX4 in shaping olfactory responses and suggest that rapid response termination and proper adaptation of peripheral sensory receptor cells tune the sensory system for optimal perception.