Spatial-temporal drivers and incidence heterogeneity of hemorrhagic fever with renal syndrome transmission in Shandong Province, China, 2016-2022.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) signals a recurring risk in Eurasia in recent years owing to its continued rise in case notifications and the extension of geographical distribution. This study was undertaken to investigate the spatiotemporal drivers and incidence heterogeneity of HFRS transmission in Shandong Province. METHODS: The epidemiological data for HFRS, meteorological data and socioeconomic data were obtained from China Information System for Disease Control and Prevention, China Meteorological Data Sharing Service System, and Shandong Statistical Yearbook, respectively. The spatial-temporal multicomponent model was employed to analyze the values of spatial-temporal components and the heterogeneity of HFRS transmission across distinct regions. RESULTS: The total effect values of the autoregressive, epidemic, and endemic components were 0.451, 0.187, and 0.033, respectively, exhibiting significant heterogeneity across various cities. This suggested a pivotal role of the autoregressive component in propelling HFRS transmission in Shandong Province. The epidemic component of Qingdao, Weifang, Yantai, Weihai, and Jining declined sharply at the onset of 2020. The random effect identified distinct incidence levels associated with Qingdao and Weifang, signifying regional variations in HFRS occurrence. CONCLUSIONS: The autoregressive component emerged as a significant driver in the transmission of HFRS in Shandong Province. Targeted preventive measures should be strategically implemented across various regions, taking into account the predominant component influencing the epidemic.

Metagenomic sequencing reveals viral diversity of mosquitoes from Shandong Province, China.

Mosquitoes carry a large number of known and unknown viruses, some of which could cause serious diseases in humans or animals. Metagenomic sequencing for mosquito viromes is crucial for understanding the evolutionary history of viruses and preventing emerging mosquito-borne diseases. We collected 1,598 mosquitoes belonging to four species from five counties in Shandong Province, China in 2021. They were grouped by species and sampling locations and subjected to metagenomic next-generation sequencing for the analysis of the viromes. A total of 233,317,352 sequencing reads were classified into 30 viral families and an unclassified group. Comparative analysis showed that mosquitoes in Shandong Province generally possessed host-specific virome. We detected mosquito-borne viruses including Japanese encephalitis virus, Getah virus, and Kadipiro virus in Culex tritaeniorhynchus and Anopheles sinensis samples. Phylogenetic analysis showed that these pathogenic viruses may have existed in mosquitoes in Shandong Province for a long time. Meanwhile, we identified 22 novel viruses belonging to seven families and the genus Negevirus. Our study comprehensively described the viromes of several common mosquito species in Shandong Province, China, and demonstrated the major role of host species in shaping mosquito viromes. Furthermore, the metagenomic data provided valuable epidemiological information on multiple mosquito-borne viruses, highlighting the potential risk of infection transmission. IMPORTANCE: Mosquitoes are known as the source of various pathogens for humans and animals. Culex tritaeniorhynchus, Armigeres subalbatus, and Anopheles sinensis have been found to transmit the Getah virus, which has recently caused increasing infections in China. Cx. tritaeniorhynchus and Culex pipiens are the main vectors of Japanese encephalitis virus and have caused epidemics of Japanese encephalitis in China in past decades. These mosquitoes are widely present in Shandong Province, China, leading to a great threat to public health and the breeding industry. This study provided a comprehensive insight into the viromes of several common mosquito species in Shandong Province, China. The metagenomic sequencing data revealed the risks of multiple pathogenic mosquito-borne viruses, including Japanese encephalitis virus, Getah virus, and Kadipiro virus, which are of great importance for preventing emerging viral epidemics.

LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway.

The excessive activation of immune responses will trigger autoimmune diseases or inflammatory injury. The endosomal sorting complexes required for transport (ESCRT) system can capture and mediate ubiquitinated protein degradation, which timely terminates signaling pathway hyperactivation. However, whether the ESCRT system participates in regulating RIGI-like receptor (RLR)-mediated antiviral responses remains unknown. In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention of viral infection.Abbreviation: 5'-pppRNA: 5' triphosphate double stranded RNA; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A1; ESCRT: endosomal sorting complexes required for transport; CHX: cycloheximide; IFIH1/MDA5: interferon induced with helicase C domain 1; IFN: interferon; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptors; RQC: ribosome-associated protein quality control; SeV: Sendai virus; TRIM27: tripartite motif-containing 27; VSV: vesicular stomatitis virus; VPS4: vacuolar protein sorting 4.

Genomic diversity and evolution analysis of severe fever with thrombocytopenia syndrome in East Asia from 2010 to 2022.

Background: Conducting an up-to-date analysis on the genomic diversity and evolution patterns of severe fever with thrombocytopenia syndrome virus (SFTSV) is crucial for elucidating the underlying mechanisms of its emergency and pathogenicity, as well as assessing the extent of its threat to public health. Methods: Complete genome sequences of SFTSV were obtained from GenBank until December 19, 2022. A thorough phylogenetic analysis was conducted using comprehensive bioinformatics methods to estimate the genomic diversity and evolution. Results: The phylogenetic classification of SFTSV strains yielded seven lineages (A-G) for each genome segment. SFTSV displayed notable variations in evolutionary patterns among different regions and segments, without a linear accumulation of nucleotide substitutions within segments and regions. The comprehensive analysis revealed 54 recombination events and 17 reassortment strains, including the first discovery of recombination events involving sea-crossing and species-crossing. Selection analysis identified three positive sites (2, 671, 1353) in RNA-dependent RNA polymerase, three positive sites (22, 298, 404) in glycoprotein, and two positive sites (9, 289) in nonstructural protein. No positive selection sites were found in nucleoprotein. Conclusion: Our study unveiled the existence of multiple evolutionary forces influencing SFTSV, contributing to its increasing genetic diversity, which had the potential to modify its antigenicity and pathogenicity. Furthermore, our study highlights the importance of tracking the spread of SFTSV across regions and species.

Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer.

Colorectal cancer is one of the malignant tumors with the highest mortality rate in the world. Survival rates vary significantly among patients at various stages of the disease. A biomarker capable of early diagnosis is required to facilitate the early detection and treatment of colorectal cancer. Human endogenous retroviruses (HERVs) are abnormally expressed in various diseases, including cancer, and have been involved in cancer development. Real-time quantitative PCR was used to detect the transcript levels of HERV-K(HML-2) gag, pol, and env in colorectal cancer to systematically investigate the connection between HERV-K(HML-2) and colorectal cancer. The results showed that HERV-K(HML-2) transcript expression was significantly higher than healthy controls and was consistent at the population and cell levels. We also used next-generation sequencing to identify and characterize HERV-K(HML-2) loci that were differentially expressed between colorectal cancer patients and healthy individuals. The analysis revealed that these loci were concentrated in immune response signaling pathways, implying that HERV-K impacts the tumor-associated immune response. Our results indicated that HERV-K might serve as a screening tumor marker and a target for tumor immunotherapy in colorectal cancer.

Transmission of SARS-CoV-2 Omicron Variant under a Dynamic Clearance Strategy in Shandong, China.

SARS-CoV-2 Omicron caused a large wave of COVID-19 cases in China in spring 2022. Shandong was one of the most affected regions during this epidemic yet was also among those areas that were able to quickly contain the transmission. We aimed to investigate the origin, genetic diversity, and transmission patterns of the Omicron epidemic in Shandong under a dynamic clearance strategy. We generated 1,149 Omicron sequences, performed phylogenetic analysis, and interpreted results in the context of available epidemiological information. We observed that there were multiple introductions of distinct Omicron sublineages into Shandong from foreign countries and other regions in China, while a small number of introductions led to majority of local cases. We found evidence suggesting that some local clusters were potentially associated with foreign imported cases. Superspreading events and cryptic transmissions contributed to the rapid spread of this epidemic. We identified a BA.1.1 genome with the R493Q reversion mutation in the spike receptor binding domain, potentially associated with an escape from vaccine and Omicron infection elicited neutralizing immunity. Our findings illustrated how the dynamic clearance strategy constrained this epidemic's size, duration, and geographical distribution. IMPORTANCE Starting in March 2022, the Omicron epidemic caused a large wave of COVID-19 cases in China. Shandong was one of the most affected regions during this epidemic but was also among those areas that were able to quickly contain the transmission. We investigated the origin, genetic diversity, and transmission patterns of Omicron epidemic in Shandong under a dynamic clearance strategy. We found that there were multiple introductions of distinct Omicron sublineages into Shandong from foreign countries and other regions in China, while a small number of introductions led to most local cases. We found evidence suggesting that some local clusters were associated with foreign imported cases. Superspreading events and cryptic transmissions contributed to the rapid spread of this epidemic. Our study illustrated the transmission patterns of Omicron epidemic in Shandong and provided a looking glass onto this epidemic in China.

Epidemiology of human papillomavirus on condyloma acuminatum in Shandong Province，China.

Condyloma acuminatum (CA) is a sexually transmitted disease (STD) caused by human papillomavirus (HPV) infection. It is important to study the prevalence and distribution of HPV genotypes before implementing the HPV vaccination program. Therefore, the aim of this study was to evaluate the epidemiological characteristics of CA cases and the distribution of HPV genotypes in Shandong Province, China. One-to-one questionnaire surveys were conducted on all patients diagnosed with CA in sentinel hospitals from Shandong Province, China. HPV genotypes were determined using the polymerase chain reaction (PCR)-reverse dot blot hybridization method. The study enrolled 1185 patients (870 males and 315 females) and found that CA patients are mainly males and sexually active people between the ages of 20 and 40. Recurrence occurred in 34.7% patients. Among the 880 CA patients who underwent HPV typing, the HPV test positivity rate was 91.4%. In these cases, low-risk (LR) HPV infection was predominant, with an infection rate of 91.3%, while high-risk (HR) HPV genotypes were found in 53.5% patients. The most frequent HPV genotypes encountered were HPV6 (57.8%), HPV11 (37.2%), HPV16 (13.7%), and HPV42 (10.3%). HPV6 and/or HPV11 are the main infections in all patients, and more than half of the patients are coinfected with HR-HPV. However, unlike other regions, HPV42 has a higher prevalence rate among CA patients in Shandong Province and is a nonvaccine HPV genotype. Therefore, regular HPV typing helps to understand the characteristics of specific genotypes and the choice of the best type for vaccine coverage.

Severe fever with thrombocytopenia syndrome virus aerosol infection in C57/BL6 mice.

Although secondary cases have become infected with the SFTSV after being in the same space without direct contact with the index case, it has not been experimentally determined if the SFTSV can be transmitted through aerosols. Here, this study aimed to verify if the SFTSV could be transmitted by aerosols. Firstly, we demonstrated that the SFTSV can infect BEAS-2B cells, and SFTSV genomes can be isolate from mild patient's sputum, which provided a foundation for the existence of SFTSV aerosol transmission. Then, we evaluated total antibody production in serum and viral load in tissue of mice infected with SFTSV by aerosols. The results showed that the presence of antibodies is related to the dose of virus infection and the SFTSV preferentially replicates in the lungs of mice following an aerosol exposure. Our study will help update the prevention and treatment guidelines for SFTSV and prevent the spread of the SFTSV in hospitals.

Spatiotemporal analysis of severe fever with thrombocytopenia syndrome in Shandong Province, China, 2014-2018.

BACKGROUND: Due to recent emergence, severe fever with thrombocytopenia syndrome (SFTS) is becoming one of the major public health problems in Shandong Province, China. The numbers of reported SFTS cases in general and the area with reported SFTS cases are both continuously increasing in recent years. However, spatiotemporal patterns and clusters of SFTS in Shandong Province have not been investigated yet. METHODS: The surveillance data of SFTS in Shandong Province, China, during 2014-2018 were extracted from China Information System for Disease Control and Prevention (CISDCP). Geoda software was used to explore spatial autocorrelation analysis, and Satscan software was used to identify spatio-temporal clustering of cases. The results were presented in ArcMap. RESULTS: The annual average incidence was 0.567/100,000 in Shandong Province during 2014-2018. Results showed that the distribution of SFTS was not random but clustered in space and time. A most likely cluster including 15 counties was observed in the northeastern region of Shandong Province from January 1, 2015 to December 31, 2015 (Relative risk = 5.13, Log likelihood ratio = 361.266, P < 0.001). CONCLUSIONS: The number of SFTS cases in Shandong Province increased overall. Geographic information system analysis coupled with spatial analysis illustrated regions with SFTS clusters. Our results provide a sound evidence base for future prevention and control programs of SFTS such as allocation of the health resources, surveillance in high-risk regions, health education, improvement of diagnosis and so on.

Analysis of the spatial-temporal components driving transmission of the severe fever with thrombocytopenia syndrome in Shandong Province, China, 2016-2018.

Existing models about the spatial-temporal distribution of the severe fever with thrombocytopenia syndrome (SFTS) entirely concentrate on aggregation, which provides limited knowledge to develop effective measures to control the epidemic of SFTS. This study aimed to identify the main spatial-temporal components and heterogeneity in different regions in Shandong Province, China. We applied the spatial-temporal multicomponent model to detect the spatial-temporal component values. A total of 2814 cases were reported from 2016 to 2018 in Shandong Province. The prevalence rate was 0.627 per 100,000, with an overall case fatality rate of 8.99%. SFTS cases were mostly clustered in central and eastern regions of Shandong Province. The total effect values of the autoregressive component, the spatiotemporal component and the endemic component were 0.586, 0.244 and 0.084, respectively, which demonstrated that the autoregressive component was the main factor driving the incidence of SFTS, followed by the spatiotemporal component. Gross domestic product per capita and weekly mean atmospheric pressure contributed to the incidence of SFTS with inverse effects. Obvious heterogeneity across regions for the autoregressive component and the spatiotemporal component was identified. In conclusion, the autoregressive and spatiotemporal components play a key role in driving the transmission of SFTS in Shandong Province. Based on the main component values, targeted measures should be formulated to control SFTS epidemics in different regions.

Severe fever with thrombocytopenia syndrome virus replicates in brain tissues and damages neurons in newborn mice.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne phlebovirus with a high fatality rate of 12-30%, which has an expanding endemic and caused thousands of infections every year. Central nervous system (CNS) manifestations are an important risk factor of SFTS outcome death. Further understanding of the process of how SFTSV invades the brain is critical for developing effective anti-SFTS encephalitis therapeutics. We obeserved changes of viral load in the brain at different time points after intraperitoneal infection of SFTSV in newborn C57/BL6 mice. The virus invaded the brain at 3 h post-infection (hpi). Notably, the viral load increased exponentially after 24 hpi. In addition, it was found that in addition to macrophages, SFTSV infected neurons and replicated in the brain. These findings provide insights into the CNS manifestations of severe SFTS, which may lead to drug development and encephalitis therapeutics.

Clinical laboratory parameters and fatality of Severe fever with thrombocytopenia syndrome patients: A systematic review and meta-analysis.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral specifically targeting SFTS virus (SFTSV) are available for the time being. Our objective was to investigate the association between clinical laboratory parameters and fatality of SFTS patients. METHODS: The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched (from inception to 24th February 2022) Web of Science, PubMed, National Knowledge Infrastructure databases and Wan Fang Data for relevant researchers on SFTS. Studies were eligible if they reported on laboratory parameters of SFTS patients and were stratified by clinical outcomes. A modified version of Newcastle-Ottawa scale was used to evaluate the quality of included studies. Standardized mean difference (SMD) was used to evaluate the association between laboratory parameters and outcomes. The between-study heterogeneity was evaluated quantitatively by standard Chi-square and the index of heterogeneity (I2). Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Publication bias was determined using funnel plots and Egger's test. RESULTS: We identified 34 relevant studies, with over 3300 participants across three countries. The following factors were strongly (SMD>1 or SMD<-0.5) and significantly (P<0.05) associated mortality: thrombin time (TT) (SMD = 1.53), viral load (SMD = 1.47), activated partial-thromboplastin time (APTT) (SMD = 1.37), aspartate aminotransferase (AST) (SMD = 1.19), lactate dehydrogenase (LDH) (SMD = 1.13), platelet count (PLT) (SMD = -0.47), monocyte percentage (MON%) (SMD = -0.47), lymphocyte percentage (LYM%) (SMD = -0.46) and albumin (ALB) (SMD = -0.43). Alanine aminotransferase, AST, creatin phosphokinase, LDH, PLT, partial-thromboplastin time and viral load contributed to the risk of dying of SFTS patients in each subgroup analyses. Sensitivity analysis demonstrated that the results above were robust. CONCLUSIONS/SIGNIFICANCE: The abnormal levels of viral load, PLT, coagulation function and liver function, significantly increase the risk of SFTS mortality, suggesting that SFTS patients with above symptoms call for special concern.

Clinical symptoms associated with fatality of severe fever with thrombocytopenia syndrome: A systematic review and meta-analysis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection disease that is deadly if left untreated. Identification of potential risk factors with prognosis value may help to focus clinical management and reduce case fatality. However, information about these factors is conflicting and scattered. In this study, documents on SFTS were collected by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Chinese Wan Fang Database through 12 January 2021. Meta-analysis was performed by using Stata and Review Manage software. 29 studies were included, involving 3011 participants with 38 clinical symptoms. The following factors were strongly (OR>5) and significantly (P-value<0.05) associated with mortality: hematemesis (OR=13.73), slurred speech (OR=5.05), disturbance of consciousness (OR=9.20), coma (OR=47.84), disseminated intravascular coagulation (OR=11.79), multiple organ dysfunction (OR=21.30), shock (OR=8.20) and acute kidney injury (OR=6.22). Non-specific symptoms, underlying diseases, respiratory symptoms and gastrointestinal symptoms were not associated with mortality of SFTS patients. Neurological symptoms and severe complications significantly increasing the death risk of SFTS cases can be identified by medical staff in resource-constrained settings and should be considered as core factors in future researchers that aim at improving the prognosis of SFTS patients.

Significant Upregulation of HERV-K (HML-2) Transcription Levels in Human Lung Cancer and Cancer Cells.

Lung cancer is the second most common cancer worldwide and the leading cause of cancer death in the world. Therefore, there is an urgent need to develop new and effective biomarkers for diagnosis and treatment. Under this circumstance, human endogenous retroviruses (HERVs) were recently introduced as novel biomarkers for cancer diagnosis. This study focused on the correlation between lung cancer and HERV-K (HML-2) transcription levels. At the cellular level, different types of lung cancer cells and human normal lung epithelial cells were used to analyze the transcription levels of the HERV-K (HML-2) gag, pol, and env genes by RT-qPCR. At the level of lung cancer patients, blood samples with background information from 734 lung cancer patients and 96 healthy persons were collected to analyze the transcription levels of HERV-K (HML-2) gag, pol, and env genes. The results showed that the transcriptional levels of the HERV-K (HML-2) gag, pol, and env genes in lung cancer cells and lung cancer patient blood samples were significantly higher than those in the healthy controls, which was also verified by RNAScope ISH technology. In addition, we also found that there was a correlation between the abnormal transcription levels of HERV-K (HML-2) genes in lung cancer patients and the clinicopathological parameters of lung cancer. We also identified the distribution locations of the gag, pol, and env primer sequences on each chromosome and analyzed the function of these loci. In conclusion, HERV-K (HML-2) genes may be a potential biomarker for the diagnosis of lung cancer.

Synergistic photodynamic/photothermal bacterial inactivation over heterogeneous quaternized chitosan/silver/cobalt phosphide nanocomposites.

Globally, drug-resistant bacteria are a potential threat to human society owing to the overuse of antibiotics and thus, non-antibiotic bactericides are urgently needed. Herein, an innovative antibacterial nanoplatform based on quaternized chitosan (QCS)/ silver (Ag)/ cobalt phosphide (CoP) nanocomposites is envisaged for achieving near-infrared (NIR) laser-inducible rapid sterilisation. In the core-shell hybrids, Ag nanoparticles (NPs) with a size of âˆ¼ 25 nm were uniformly deposited on CoP nanoneedles, upon which a layer of QCS (approximately 10 wt%), is coated. Numerical calculations revealed that under NIR irradiation, high-energy hot electrons arising from the surface plasmon resonance effect of Ag migrate into the interface between Ag and CoP, and amplify the photothermal effect of CoP. Meanwhile, photo-excited electrons from CoP are transported onto Ag NPs because the Schottky heterostructure facilitates the production of reactive oxygen species. Ag loading simultaneously enhances the photocatalytic and photothermal effects of CoP, achieving rapid antibacterial activity synergistically. The QCS coating improves the dispersibility of power in an aqueous system and provides contact between the antiseptics and bacteria. The ternary QCS/Ag/CoP nanocomposites achieved greater than 99.6% inactivation against S. aureus and E. coli within 10 min. In addition, the nanocomposites were confirmed to be noncytotoxic to mammals. Consequently, the QCS/Ag/CoP nanoplatforms possess great potential for rapid and effective antibacterial applications.

Scoring Model for Predicting the Occurrence of Severe Illness in Hospitalized Patients with Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with high mortality. Severe cases progressed rapidly, with deaths occurring within 2 weeks. Therefore, constructing a model to predict disease progression among hospitalized patients plays an important role in clinical practice. The development cohort included 121 patients with SFTS, 25 with severe SFTS, and 96 with mild SFTS. Two of the 64 variables were independent risk factors, including neurological symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 3.342-49.916; P < 0.001) and aspartate aminotransferase/alanine aminotransferase levels (OR, 1.891; 95% CI, 1.272-2.813; P = 0.002). The model's area under the curve (AUC) was 0.882 (95% CI: 0.808-0.956). The mean AUC value obtained from the internal validation was 0.883 (95% CI: 0.809-0.957). The AUC in the external validation cohort was 0.873 (95% CI: 0.775-0.972). This model can be used to identify severely ill patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians with their treatment plans.

Metagenomic next-generation sequencing identified psittacosis among poultry processing workers in Shandong Province, China.

Human infection with Chlamydia psittaci is rare but difficult to recognize. We report an outbreak of psittacosis among poultry processing workers in China. We applied metagenomic next-generation sequencing and identified Chlamydia psittaci reads from samples of all seven patients, four of which were subsequently confirmed by PCR. Epidemiological results suggested that the poultry processed in the factory was the possible source of human infection.

Roles of conserved residues in the receptor binding sites of human parainfluenza virus type 3 HN protein.

Human parainfluenza virus type 3 (hPIV-3) entry and intrahost spread through membrane fusion are initiated by two envelope glycoproteins, hemagglutinin-neuraminidase (HN) and fusion (F) protein. Binding of HN protein to the cellular receptor via its receptor-binding sites triggers conformational changes in the F protein leading to virus-cell fusion. However, little is known about the roles of individual amino acids that comprise the receptor-binding sites in the fusion process. Here, residues R192, D216, E409, R424, R502, Y530 and E549 located within the receptor-binding site Ⅰ, and residues N551 and H552 at the putative site Ⅱ were replaced by alanine with site-directed mutagenesis. All mutants except N551A displayed statistically lower hemadsorption activities ranging from 16.4% to 80.2% of the wild-type (wt) level. With standardization of the number of bound erythrocytes, similarly, other than N551A, all mutants showed reduced fusogenic activity at three successive stages: lipid mixing (hemifusion), content mixing (full fusion) and syncytium development. Kinetic measurements of the hemifusion process showed that the initial hemifusion extent for R192A, D216A, E409A, R424A, R502A, Y530A, E549A and H552A was decreased to 69.9%, 80.6%, 71.3%, 67.3%, 50.6%, 87.4%, 84.9% and 25.1%, respectively, relative to the wt, while the initial rate of hemifusion for the E409A, R424A, R502A and H552A mutants was reduced to 69.0%, 35.4%, 62.3%, 37.0%, respectively. In addition, four mutants with reduced initial hemifusion rates also showed decreased percentages of F protein cleavage from 43.4% to 56.3% of the wt. Taken together, Mutants R192A, D216A, E409A, R424A, R502A, Y530A, E549A and H552A may lead to damage on the fusion activity at initial stage of hemifusion, of which decreased extent and rate may be associated with impaired receptor binding activity resulting in the increased activation barrier of F protein and the cleavage of it, respectively.

Research progress on coronavirus S proteins and their receptors.

Coronaviruses are a large family of important pathogens that cause human and animal diseases. At the end of 2019, a pneumonia epidemic caused by a novel coronavirus brought attention to coronaviruses. Exploring the interaction between the virus and its receptor will be helpful in developing preventive vaccines and therapeutic drugs. The coronavirus spike protein (S) plays an important role in both binding to receptors on host cells and fusion of the viral membrane with the host cell membrane. This review introduces the structure and function of the S protein and its receptor, focusing on the binding mode and binding region of both.