Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.DOI: http://dx.doi.org/10.7554/eLife.00049.001
We investigate the evolution of NOAA Active Region 11817 during 2013 August 10-12, when it developed a complex field configuration and produced four confined, followed by two eruptive, flares. These C-and-above flares are all associated with a magnetic flux rope (MFR) located along the major polarity inversion line, where shearing and converging photospheric flows are present. Aided by the nonlinear force-free field modeling, we identify the MFR through mapping magnetic connectivities and computing the twist number T w for each individual field line. The MFR is moderately twisted (|T w | < 2) and has a well-defined boundary of high squashing factor Q. We found that the field line with the extremum |T w | is a reliable proxy of the rope axis, and that the MFR's peak |T w | temporarily increases within half an hour before each flare while it decreases after the flare peak for both confined and eruptive flares. This pre-flare increase 9 Max-Planck-Institut für Sonnensystemforschung, Justus-von-Liebig-Weg 3, 37077 Göttingen, Germany -2 -in |T w | has little effect on the active region's free magnetic energy or any other parameters derived for the whole region, due to its moderate amount and the MFR's relatively small volume, while its decrease after flares is clearly associated with the stepwise decrease in the whole region's free magnetic energy due to the flare. We suggest that T w may serve as a useful parameter in forewarning the onset of eruption, and therefore, the consequent space weather effects. The helical kink instability is identified as the prime candidate onset mechanism for the considered flares.
We have observed the fine temporal and spatial structure of a filament eruption on 2002 May 27 following an M2-class flare. Our observations at Big Bear Solar Observatory were made at the wavelength of Ha 1.3 Å , with a cadence of 40 ms. The event was also observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) at X-ray energies from 3 to 50 keV and by the Transition Region and Coronal Explorer (TRACE) in poFe xii 195 Å . The event appears to be a "failed eruption," as the filament material, seen in absorption by TRACE, first accelerated then decelerated as it approached its peak height of ∼ km while 4 8 # 10 the filament threads drained back to the Sun. The fact that the eruption did not lead to a coronal mass ejection indicates that the coronal magnetic field near ∼ km did not open during the flare. The height-time curve 4 8 # 10 obtained from the TRACE 195 Å images during the deceleration phase shows that the deceleration of the filament exceeded the gravitational deceleration by more than a factor of 10, which suggests that the filament material was pulled back by magnetic tension. Also of importance are three sequential but cospatial features-brightenings in EUV, a loop-top hard X-ray emission, and "rupturing" of the Ha filament-that point to a release of energy (and probably magnetic reconnection) above the initial filament's location but well below its terminal height. Reconnection above a filament does not appear in most models, with the notable exception of quadrupolar and "breakout" models. These observations provide evidence that at least two conditions are required for a successful eruption: a reconnection very low in the corona (possibly above the filament) and open or opening fields above that point.
An observational relationship has been well established among magnetic reconnection, high-energy flare emissions and the rising motion of erupting flux ropes. In this paper, we verify that the rate of magnetic reconnection in the low corona is temporally correlated with the evolution of flare nonthermal emissions in hard X-rays and microwaves, all reaching their peak values during the rising phase of the soft X-ray emission. In addition, however, our new observations reveal a temporal correlation between the magnetic reconnection rate and the directly observed acceleration of the accompanying coronal mass ejection (CME) and filament in the low corona, thus establishing a correlation with the rising flux rope. These results are obtained by examining two well-observed two-ribbon flare events, for which we have good measurements of the rise motion of filament eruption and CMEs associated with the flares. By measuring the magnetic flux swept through by flare ribbons as they separate in the lower atmosphere, we infer the magnetic reconnection rate in terms of the reconnection electric field E rec inside the reconnecting current sheet (RCS) and the rate of magnetic flux convected into the diffusion region. For the X1.6 flare event, the inferred E rec is~5.8 V cm À1 and the peak mass acceleration is 3 km s À2 , while for the M1.0 flare event E rec is~0.5 V cm À1 and the peak mass acceleration is 0.2-0.4 km s À2 .
A systematic motion of Ha kernels during solar Ñares can be regarded as the chromospheric signature of progressive magnetic reconnection in the corona, in that the magnetic Ðeld lines swept through by the kernel motion are those connected to the di †usion region at the reconnection point. In this paper, we present high-cadence and high-resolution Ha[1.3 observations of an impulsive Ñare that exhibits a A systematic kernel motion and relate them to the reconnecting current sheet (RCS) in the corona. Through analyses of X-ray and microwave observations, we further examine the role of the macroscopic electric Ðeld inside the RCS in accelerating electrons. We measure the velocity of the kernel motion to be 20[100 km s~1. This is used together with the longitudinal magnetic Ðeld to infer an electric Ðeld as high as 90 V cm~1 at the Ñare maximum. This event shows a special magnetic Ðeld conÐguration and motion pattern of Ha kernels, in that a light bridge divides a Ñare kernel into two parts that move in di †erent manners : one moving into the stronger magnetic Ðeld and the other moving along the isogauss contour of the longitudinal magnetic Ðeld. The temporal variation of the electric Ðeld inferred from the former type of kernel motion is found to be correlated with 20È85 keV hard X-ray light curves during the rise of the major impulsive phase. This would support the scenario of magnetic energy release via current dissipation inside the RCS, along with the hypothesis of the DC electric Ðeld acceleration of X-rayÈemitting electrons below 100 keV. However, there is no good temporal correlation between the hard X-ray emission and the inferred electric Ðeld from the other motion pattern. Furthermore, the microwave emission, which supposedly comes from higher energy electrons, shows a time proÐle and electron spectrum that di †ers from those of the X-ray bursts. We conclude that either the twodimensional magnetic reconnection theory related to the Ha kernel motion is applicable to only some part of the Ñare region due to its special magnetic geometry, or the electron acceleration is dominated by other mechanisms depending on the electron energy.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused >20 million infections and >750,000 deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has been found closely related to the bat coronavirus strain RaTG13 (Bat-CoV RaTG13) and a recently identified pangolin coronavirus (Pangolin-CoV-2020). Here we first investigated the ability of SARS-CoV-2 and three related coronaviruses to utilize animal orthologs of angiotensin-converting enzyme 2 (ACE2) for cell entry. We found that ACE2 orthologs of a wide range of domestic and wild mammals, including camels, cattle, horses, goats, sheep, cats, rabbits and pangolins, were able to support cell entry of SARS-CoV-2, suggesting that these species might be able to harbor and spread this virus. In addition, the pangolin and bat coronaviruses, Pangolin-CoV-2020 and Bat-CoV RaTG13, were also found able to utilize human ACE2 and a number of animal-ACE2 orthologs for cell entry, indicating risks of spillover of these viruses into humans in the future. We then developed potently anti-coronavirus ACE2-Ig proteins that are broadly effective against the four distinct coronaviruses. In particular, through truncating ACE2 at its residue 740 but not 615, introducing a D30E mutation, and adopting an antibody-like tetrameric-ACE2 configuration, we generated an ACE2-Ig variant that neutralizes SARS-CoV-2 at picomolar range. These data demonstrate that the improved ACE2-Ig variants developed in this study could potentially be developed to protect from SARS-CoV-2 and some other SARS-like viruses that might spillover into humans in the future. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the currently uncontrolled coronavirus disease 2019 (COVID-19) pandemic. It is important to study the host range of SARS-CoV-2 because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. In this study, we found that ACE2 orthologs of a wide range of domestic and wild animals can support cell entry of SARS-CoV-2 and three related coronaviruses, providing insights into identifying animal hosts of these viruses. We also developed recombinant ACE2-Ig proteins that are able to potently block these viral infections, providing a promising approach to developing antiviral proteins broadly effective against these distinct coronaviruses.
We have studied the evolution of the photospheric magnetic Ðeld in active region NOAA 8668 for 3 days while the formation of a reverse S-shaped Ðlament proceeded. From a set of full-disk line-of-sight magnetograms taken by the Michelson Doppler Imager (MDI) on board the Solar and Heliospheric Observatory (SOHO), we have found a large canceling magnetic feature that was closely associated with the formation of the Ðlament. The positive Ñux of the magnetic feature was initially 1.5 ] 1021 Mx and exponentially decreased with an e-folding time of 28 hr throughout the period of observations. We also have determined the transverse velocities of the magnetic Ñux concentrations in the active region by applying local correlation tracking. As a result, a persistent pattern of shear motion was identiÐed in the neighborhood of the Ðlament. The shear motion had a speed of 0.2È0.5 km s~1 and fed negative magnetic helicity of [3 ] 1042 Mx2 into the coronal volume during an observing run of 50 hr at an average rate of [6 ] 1040 Mx2 hr~1. This rate is an order of magnitude higher than the rate of helicity change due to the solar di †erential rotation. The magnetic Ñux of the Ðeld lines created by magnetic reconnection and the magnetic helicity generated by the photospheric shear motion are much more than enough for the formation of the Ðlament. Based on this result, we conjecture that the Ðlament formation may be the visible manifestation of the creation of a much bigger magnetic structure that may consist of a Ñux rope and an overlying sheared arcade.
Solar flare emissions in the chromosphere often appear as elongated ribbons on both sides of the magnetic polarity inversion line (PIL), which has been regarded as evidence of a typical configuration of magnetic reconnection. However, flares having a circular ribbon have rarely been reported, although it is expected in the fan-spine magnetic topology involving reconnection at a three-dimensional (3D) coronal null point. We present five circular ribbon flares with associated surges, using high-resolution and high-cadence Hα blue wing observations obtained from the recently digitized films of Big Bear Solar Observatory. In all the events, a central parasitic magnetic field is encompassed by the opposite polarity, forming a circular PIL traced by filament material. Consequently, a flare kernel at the center is surrounded by a circular flare ribbon. The four homologous jet-related flares on 1991 March 17 and 18 are of particular interest, as (1) the circular ribbons brighten sequentially, with co-spatial surges, rather than simultaneously, (2) the central flare kernels show an intriguing "round-trip" motion and become elongated, and (3) remote brightenings occur at a region with the same magnetic polarity as the central parasitic field and are co-temporal with a separate phase of flare emissions. In another flare on 1991 February 25, the circular flare emission and surge activity occur successively, and the event could be associated with magnetic flux cancellation across the circular PIL. We discuss the implications of these observations combining circular flare ribbons, homologous jets, and remote brightenings for understanding the dynamics of 3D magnetic restructuring.
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