In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

[Q]: A new porcine coronavirus SADS-CoV was recently identified from suckling piglets 20 with severe diarrhea in southern China and its genome sequence is most identical (~95% 21 identity) to that of bat -coronavirus HKU2. It again indicates bats are the natural 22 reservoir of many coronaviruses that have great potential for cross-species transmission 23 to animals and humans by recombination and/or mutation. Here we report the cryo-EM 24 structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 A and 2.83 A 25 resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural 26 similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 27 subunit responsible for cell attachment and receptor binding. We systematically 28 analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and 29 the S2 subunit of HKU2 spike with those of -, -, -, and -coronavirus spikes. The 30 results show that the NTD and CTD of HKU2/SADS-CoV are probably the most 31 ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion 32 is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV 33 S2 subunit also adopts a conformation distinct from other coronaviruses. These results 34 structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV 35 and -coronavirus spikes and provide new insights into the evolution and cross-species 36 transmission of coronaviruses. : bioRxiv preprint 39 Coronaviruses, categorized into the order Nidovirales family Coronaviridae and 40 subfamily Coronavirinae, are a large group of viral pathogens with a wide host range 1 . 41 Their infections in humans, other mammals and birds can cause respiratory, hepatic, 42 enteric and neurological diseases with varying severity 2 . The severe acute respiratory 43 syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus 44 (MERS-CoV) have posed severe threats to human health in the 21 st century 1,3 . In the 45 meantime, coronaviruses infecting domestic animals also bring substantial economic 46 losses 4 . For example, the swine acute diarrhea syndrome coronavirus (SADS-CoV) 47 (also known as SeACoV and PEAV) isolated in 2017 caused outbreaks of severe watery 48 diarrhea of suckling piglets with a mortality up to 90% in several commercial pig farms 49 in Guangdong Province of China 5-10 . SADS-CoV is an -coronavirus and other 50 representative members in the -genus are porcine epidemic diarrhea virus 51 (PEDV), porcine transmissible gastroenteritis coronavirus (TGEV), porcine respiratory 52 coronavirus (PRCV), human NL63 and 229E coronaviruses (HCoV-NL63 and HCoV-53 229E) 1 . Representative members in other three genera include mouse hepatitis 54 coronavirus (MHV), bovine coronavirus (BCoV), SARS-CoV, MERS-CoV, HCoV-55 OC43 and HCoV-HKU1 in the -genus, avian infectious bronchitis virus (IBV) in the 56 -genus and porcine deltacoronavirus (PdCoV) in the -genus 1 . 57 Cross-species transmission promoted by genetic recombination and/or mutations 58 underlies the host range expansion of coronaviruses 3,11-13 . Bats are the natural reservoir 59 of more than 30 different -and -coronaviruses that have great potential for 60 interspecies transmission by recombination and/or mutation 12,14-16 . Data on genetic 61 evolution, receptor binding and pathogenesis have demonstrated that human SARS-62 CoV and MERS-CoV most likely originate from bats 1 . Palm civets and dromedary 63 camels are the intermediate hosts of SARS-CoV and MERS-CoV from bats to humans 1 , 64 respectively. The newly identified porcine SADS-CoV isolates are also found to share 65 ~95% sequence identity with Rhinolophus bat coronavirus HKU2, and this further 66 stressed the severe results of coronavirus spillover from bats to domestic animals 5-10 .
[A]: Cryo-EM structures of HKU2 and SADS-CoV spike 1 glycoproteins and insights into coronavirus evolution 2 3 4

[Q]: The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) virus is a major problem since it evades the function of antibodies and chemical inhibitors. Here, we demonstrate a viral detection strategy based on synthetic biology principles to detect a specific viral function rather than a particular viral protein. The resistance caused by mutations can be circumvented since the mutations that cause the loss of function also incapacitate the virus. Many pathogens encode proteases that are essential for their replication and that have a defined substrate specificity. A genetically encoded sensor composed of a fused membrane anchor, viral protease target site, and an orthogonal transcriptional activator was engineered into a human cell line. The HIV-1 protease released the transcriptional activator from the membrane, thereby inducing transcription of the selected genes. The device was still strongly activated by clinically relevant protease mutants that are resistant to protease inhibitors. In the future, a similar principle could be applied to detect also other pathogens and functions.
[A]: Function-Based Mutation-Resistant Synthetic Signaling Device Activated by HIV-1 Proteolysis

[Q]: The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4 + CD25 + Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. Key parameters for infection outcome in E. multilocularis-infected fgl2 -/-(AE-fgl2 -/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4 + CD25 + Treg suspensions were incubated with CD4 + effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune PLOS Neglected Tropical Diseases | responses and maturation of dendritic cells. We showed that AE-fgl2 -/mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation. FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases. In larval E. multilocularis infection causing alveolar echinococcosis (AE) in humans as well as mice, immune tolerance and/or down-regulation of protective immunity is a marked characteristic of this chronic disease. Our study provides a comprehensive evidence for a major involvement of the recently identified CD4 + CD25 + Regulatory T Cell Effector Molecule FGL2 to the outcome of AE. Our major findings are as follows: 1) FGL2 is mostly secreted by Tregs and partly contributes to their functions; 2) FGL2 can downregulate the maturation of DCs, suppress Th1 and Th17 immune responses, and support Th2 and Treg immune responses, and finally 3) IL-17A contributes to FGL2 secretion. Based on the present findings in mice, we will investigate FGL2 as a potential marker of progression of AE in human patients, or as a potential immunotherapeutical target. Early prediction of parasite regression (currently not yet possible) would allow clinicians to plan for withdrawing benzimidazole treatment, which is currently administered for life. Then, FGL2 should be investigated as a target for an anticipated immunomodulatory treatment of patients with progressive AE, especially of those who are non-or low-responders to benzimidazole treatment, or who suffer from side-effects due to chemotherapy. FGL2 in Murine Alveolar Echinococcosis PLOS Neglected Tropical Diseases |
[A]:
Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4 + CD25 + Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice