Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of adenosine 5′-triphosphate (ATP), which acts as a neurotransmitter to activate afferent neural gustatory pathways1. However, how ATP is released to fulfill this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel2,3, is indispensable for taste stimuli-evoked ATP release from sweet-, bitter- and umami-sensing taste bud cells. Calhm1 knockout mice have severely impaired perceptions of sweet, bitter and umami compounds, whereas sour and salty taste recognition remains mostly normal. Calhm1 deficiency affects taste perception without interfering with taste cell development or integrity. CALHM1 is expressed specifically in sweet/bitter/umami-sensing type II taste bud cells. Its heterologous expression induces a novel ATP permeability that releases ATP from cells in response to manipulations that activate the CALHM1 ion channel. Knockout of Calhm1 strongly reduces voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells to taste stimuli. Thus, CALHM1 is a voltage-gated ATP release channel required for sweet, bitter and umami taste perception.

Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two , the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.

Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses with genome sizes of approximately 30 kb. They belong to the family Coronaviridae in the order Nidovirales and are currently classified into four major genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus (1). Coronaviruses can infect a wide range of mammals, as well as birds (2). The broad species tropism is predominantly attributed to the high diversity in receptor usage across different coronaviruses. To date, six coronaviruses are known to infect humans, and they utilize different surface molecules for cell entry. In particular, human coronavirus 229E (HCoV-229E) binds aminopeptidase N (APN) (3), and human coronavirus OC43 (HCoV-OC43) binds O-acetylated sialic acid (4). Severe acute respiratory syndrome coronavirus (SARS-CoV) (5) and human coronavirus NL63 (HCoV-NL63) (6) both bind angiotensin I converting enzyme 2 (ACE2). The receptor for human coronavirus HKU1 (HCoV-HKU1) has not been defined. However, O-acetylated sialic acid has been suggested as an attachment factor that contributes to the binding of HCoV-HKU1 to the cell surface (7). Middle East respiratory syndrome coronavirus (MERS-CoV) is the sixth coronavirus known to cause infection in humans (8). Intriguingly, MERS-CoV utilizes a unique cellular receptor, dipeptidyl peptidase 4 (DPP4), for virus entry (9). The host cell receptors for a number of animal coronaviruses have also been identified. For instance, porcine transmissible gastroenteritis coronavirus (TGEV) binds APN (10), and the prototype betacoronavirus mouse hepatitis virus (MHV) uses

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Staphylococcus lugdunensis is a member of the coagulase-negative staphylococci and commonly found as part of the human skin flora. It is a significant cause of catheter-related bacteremia and also causes serious infections like native valve endocarditis in previously healthy individuals. We report the complete genome sequence of this medically important bacterium.