Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Background:The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome-related coronavirus-2(SARS-CoV-2)is pandemic.However,the origins and global transmission pattern of SARS-CoV-2 remain largely unknown.We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics.Methods:Using the full-length sequences of SARS-CoV-2 with intact geographic,demographic,and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020,we constructed the transmission tree to depict the evolutionary process by the R package"outbreaker".The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2(ACE2)was predicted using mCSM-PPI2 software.Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test.Results:From 26 December 2019 to 8 March 2020,early stage of the COVID-19 pandemic,SARS-CoV-2 strains identified worldwide were mainly composed of three clusters:the Europe-based cluster including two USA-based subclusters;the Asia-based cluster including isolates in China,Japan,the USA,Singapore,Australia,Malaysia,and Italy;and the USA-based cluster.The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade.After 8 March 2020,the clusters of SARS-CoV-2 strains tended to be independent and became"pure"in each of the major countries.Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2.Of all predicted mutants,the number of E484K was the largest one with 86585 sequences,followed by S477N with 55442 sequences worldwide.In more than ten countries,the frequencies of the isolates with E484K and S477N increased significantly.V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses(P<0.001).SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart(P<0.001).Conclusions:SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure.Travel restrictions might cause location-specific SARS-CoV-2 clustering.The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion.

Study on the Microscopic Network Model of PVA Hydrogel Based on the Tensile Behavior

Hydrogel is an emerging material widely used in the biological field.The tensile properties of hydrogel mainly depend on its polymer network,but due to the complex microstructure of the network,some properties of the hydrogel have yet to be qua nt itatively analyzed.In this article,we built a three-dimensional random fiber net work to characterize the micros tructure of a hydrogel.The fibers were simplified as elastic beams,and the cross-links were regarded as"hinges."Combined with the macroscopic experimental results,the influence of the change of fiber length and the relationship between the polymer content and the cross-link density were studied.The model was verified by the quasi-static tensile test results of real PVA hydrogel materials with different fiber contents.The results show that the model can well match the tensile stress-strain curve and tensile strength of the PVA hydrogels with different fiber contents.The change in micros true ture of the fiber network induces nonlinear behaviors,and although the cross-link number increases with the increase in polymer content,the cross-link density(per unit PVA chain length)of the PVA hydrogel slightly decreases as the content increases.

Association of human leukocyte antigen-DR-DQ-DP haplotypes with the risk of hepatitis B virus-related hepatocellular carcinoma

Aim:Genetic polymorphisms of human leukocyte antigen(HLA)class II molecules are associated with chronic hepatitis B virus(HBV)infection.We aimed to investigate the impacts of HLA-II haplotypes on viral evolution and the risks of HBV-caused liver diseases.Methods:HLA-DR-DQ-DP haplotypes were estimated in 1210 healthy controls,296 HBV clearance subjects,301 asymptomatic hepatitis B surface antigen carriers,770 chronic hepatitis B patients,443 HBV-related liver cirrhosis(LC)patients,and 1037 HBV-related hepatocellular carcinoma(HCC)patients.HBV mutations were determined by sequencing.The associations of HLA-DR-DQ-DP haplotypes with viral mutations and the risks of liver diseases were assessed by multivariate logistic regression.Results:Compared to HBV-free subjects,the haplotypes CCAACG,CCGACG,TCAATA,and TCGATA were associated with decreased HCC risk,with an odds ratio(OR)[95%confidence interval(CI)]of 0.62(0.40-0.95),0.60(0.39-0.92),0.73(0.54-0.98),and 0.58(0.42-0.78),respectively.CCAACG,CCGACG,and TCAATA were significantly associated with decreased frequencies of the HCC-risk HBV mutations:preS1 deletion,APOBECsignature HBV mutations in the core promoter and preS regions,A51C/T,G104C/T,and G146C/T.TCGATA and TTAACG were associated with increased LC risk,with an OR(95%CI)of 1.54(1.03-2.30)and 2.23(1.50-3.33),respectively.However,TCGATA and TTAACG were not consistently associated with the cirrhosis-risk HBV mutations.Conclusion:CCAACG,CCGACG,and TCAATA are inversely associated with HCC risk,possibly because they are involved in creating an immune microenvironment attenuating the generation of HCC-risk HBV mutations.TCGATA and TTAACG might predispose the polarity of immunity towards Th17 isotype related to LC.

A brief on the current occurrence of Gorsachius spp.in China's Mainland

So far, three species of night herons have been recorded in China, the White-eared Night Heron （Gorsachius magnificus）, the Japanese Night Heron （G. goisagi）, and the Malayan Night Neron （G. melanolophus）.