An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism.

Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health

Insight into the Interaction of Metal Ions with TroA from Streptococcus suis

The scavenging ability of sufficient divalent metal ions is pivotal for pathogenic bacteria to survive in the host. ATP-binding cassette (ABC)-type metal transporters provide a considerable amount of different transition metals for bacterial growth. TroA is a substrate binding protein for uptake of multiple metal ions. However, the function and structure of the TroA homologue from the epidemic Streptococcus suis isolates (SsTroA) have not been characterized.Here we determined the crystal structure of SsTroA from a highly pathogenic streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis in complex with zinc. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that apo-SsTroA binds Zn(2+) and Mn(2+). Both metals bind to SsTroA with nanomolar affinity and stabilize the protein against thermal unfolding. Zn(2+) and Mn(2+) induce distinct conformational changes in SsTroA compared with the apo form as confirmed by both circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra. NMR data also revealed that Zn(2+)/Mn(2+) bind to SsTroA in either the same site or an adjacent region. Finally, we found that the folding of the metal-bound protein is more compact than the corresponding apoprotein.Our findings reveal a mechanism for uptake of metal ions in S. suis and this mechanism provides a reasonable explanation as to how SsTroA operates in metal transport

Roughness of Interfacial Crack Front: Correlated Percolation in the Damage Zone

We show that the roughness exponent zeta of an in-plane crack front slowly propagating along a heterogeneous interface embeded in a elastic body, is in full agreement with a correlated percolation problem in a linear gradient. We obtain zeta=nu/(1+nu) where nu is the correlation length critical exponent. We develop an elastic brittle model based on both the 3D Green function in an elastic half-space and a discrete interface of brittle fibers and find numerically that nu=1.5, We conjecture it to be 3/2. This yields zeta=3/5. We also obtain by direct numerical simulations zeta=0.6 in excellent agreement with our prediction. This modelling is for the first time in close agreement with experimental observations.Comment: 4 pages RevTeX

Inference of person-to-person transmission of COVID-19 reveals hidden super-spreading events during the early outbreak phase

Coronavirus disease 2019 (COVID-19) was first identified in late 2019 in Wuhan, Hubei Province, China and spread globally in months, sparking worldwide concern. However, it is unclear whether super-spreading events occurred during the early outbreak phase, as has been observed for other emerging viruses. Here, we analyse 208 publicly available SARS-CoV-2 genome sequences collected during the early outbreak phase. We combine phylogenetic analysis with Bayesian inference under an epidemiological model to trace person-to-person transmission. The dispersion parameter of the offspring distribution in the inferred transmission chain was estimated to be 0.23 (95% CI: 0.13–0.38), indicating there are individuals who directly infected a disproportionately large number of people. Our results showed that super-spreading events played an important role in the early stage of the COVID-19 outbreak

Macrophage-Tropic HIV Induces and Exploits Dendritic Cell Chemotaxis

Immature dendritic cells (iDCs) express the CC chemokine receptor (CCR)5, which promotes chemotaxis toward the CC chemokines regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β. By contrast, mature DCs downregulate CCR5 but upregulate CXC chemokine receptor (CXCR)4, and as a result exhibit enhanced chemotaxis toward stromal cell–derived factor (SDF)-1α. CCR5 and CXCR4 also function as coreceptors for macrophage-tropic (M-tropic) and T cell–tropic (T-tropic) human immunodeficiency virus (HIV)-1, respectively. Here, we demonstrate chemotaxis of iDCs toward M-tropic (R5) but not T-tropic (X4) HIV-1. Furthermore, preexposure to M-tropic HIV-1 or its recombinant envelope protein prevents migration toward CCR5 ligands. The migration of iDCs toward M-tropic HIV-1 may enhance formation of DC–T cell syncytia, thus promoting viral production and destruction of both DC and T helper lymphocytes. Therefore, disturbance of DC chemotaxis by HIV-1 is likely to contribute to immunosuppression in primary infection and AIDS. In addition, migration of iDCs toward HIV-1 may aid the capture of R5 HIV-1 virions by the abundant DC cell surface protein DC-specific intercellular adhesion molecule (ICAM)3-grabbing nonintegrin (DC-SIGN). HIV-1 bound to DC cell–specific DC-SIGN retains the ability to infect replication-permissive T cells in trans for several days. Consequently, recruitment of DC by HIV-1 could combine with the ability of DC-SIGN to capture and transmit the virus to T cells, and so facilitate dissemination of virus within an infected individual

Structural Analysis of Alkaline β-Mannanase from Alkaliphilic Bacillus sp. N16-5: Implications for Adaptation to Alkaline Conditions

Significant progress has been made in isolating novel alkaline β-mannanases, however, there is a paucity of information concerning the structural basis for alkaline tolerance displayed by these β-mannanases. We report the catalytic domain structure of an industrially important β-mannanase from the alkaliphilic Bacillus sp. N16-5 (BSP165 MAN) at a resolution of 1.6 Å. This enzyme, classified into subfamily 8 in glycosyl hydrolase family 5 (GH5), has a pH optimum of enzymatic activity at pH 9.5 and folds into a classic (β/α)8-barrel. In order to gain insight into molecular features for alkaline adaptation, we compared BSP165 MAN with previously reported GH5 β-mannanases. It was revealed that BSP165 MAN and other subfamily 8 β-mannanases have significantly increased hydrophobic and Arg residues content and decreased polar residues, comparing to β-mannanases of subfamily 7 or 10 in GH5 which display optimum activities at lower pH. Further, extensive structural comparisons show alkaline β-mannanases possess a set of distinctive features. Position and length of some helices, strands and loops of the TIM barrel structures are changed, which contributes, to a certain degree, to the distinctly different shaped (β/α)8-barrels, thus affecting the catalytic environment of these enzymes. The number of negatively charged residues is increased on the molecular surface, and fewer polar residues are exposed to the solvent. Two amino acid substitutions in the vicinity of the acid/base catalyst were proposed to be possibly responsible for the variation in pH optimum of these homologous enzymes in subfamily 8 of GH5, identified by sequence homology analysis and pKa calculations of the active site residues. Mutational analysis has proved that Gln91 and Glu226 are important for BSP165 MAN to function at high pH. These findings are proposed to be possible factors implicated in the alkaline adaptation of GH5 β-mannanases and will help to further understanding of alkaline adaptation mechanism

Assessing the extent of community spread caused by mink-derived SARS-CoV-2 variants

SARS-CoV-2 has recently been found to have spread from humans to minks and then to have transmitted back to humans. However, it is unknown to what extent the human-to-human transmission caused by the variant has reached. Here, we used publicly available SARS-CoV-2 genomic sequences from both humans and minks collected in Denmark and Netherlands, and combined phylogenetic analysis with Bayesian inference under an epidemiological model to trace the possibility of person-to-person transmission. The results showed that at least 12.5% of all people being infected with dominated mink-derived SARS-CoV-2 variants in Denmark and Netherlands were caused by human-to-human transmission, indicating this “back-to-human” SARS-CoV-2 variant has already caused human-to-human transmission. Our study also indicated the need for monitoring this mink-derived and other animal source “back-to-human” SARS-CoV-2 in future and that prevention and control measures should be tailored to avoid large-scale community transmission caused by the virus jumped between animals and humans

Purely-long-range bound states of He(2s3S)+(2s ^3S)+He(2p3P)(2p ^3P)

We predict the presence and positions of purely-long-range bound states of $^4$He$(2s ^3S)+{}^4$He$(2p ^3P)$ near the $2s ^3S_1+2p ^3P_{0,1}$ atomic limits. The results of the full multichannel and approximate models are compared, and we assess the sensitivity of the bound states to atomic parameters characterizing the potentials. Photoassociation to these purely-long-range molecular bound states may improve the knowledge of the scattering length associated with the collisions of two ultracold spin-polarized $^4$He$(2s ^3S)$ atoms, which is important for studies of Bose-Einstein condensates.Comment: 16 pages, 5 figure