The emulation of characteristics of a different organism to gain biological advantage is a common phenomenon in nature,described and defined with the term"mimicry"in the second half of the 19th century.In th...The emulation of characteristics of a different organism to gain biological advantage is a common phenomenon in nature,described and defined with the term"mimicry"in the second half of the 19th century.In the last decades,mimicry at molecular level has been evidenced as a method used by several pathogen microrganisms to control metabolic functions of infected cells and elude host’s immune system.Because of molecular mimicry,immune reactions against microbial molecules can turn against the mimicked self-molecules in predisposed subjects,leading to autoimmunity.This pathogenic mechanism,which gives a possible explanation for the specific epidemiological and chronological association between some infections and some autoimmune diseases,is well known and verified in many fields of medicine,but not adequately studied in dermatology:experimental data are available only for leprosy,atopic dermatitis,Beh?et’s disease,Vogt-Koyanagi-Harada syndrome and systemic erythematous lupus,while for few other diseases its role is hypothetical or suggested on the basis of single,small experiments or anecdotal reports.An overview of available data and hypotheses about the role of molecular mimicry in autoimmune cutaneous diseases is presented here,together with the perspectives offered by the use of bioinformatics and the personal experi-ence of the author in this field.展开更多
The cleavability of the hemagglutinin (HA) plays a major role in virulence of avian influenza viruses. Detailed analyses of the cleavage sequences and their evolution would give insights into the high pathogenicity of...The cleavability of the hemagglutinin (HA) plays a major role in virulence of avian influenza viruses. Detailed analyses of the cleavage sequences and their evolution would give insights into the high pathogenicity of the H5N1 virus. HA segments were visually identifiable in the cellular automata (CA) image, and a feature gene segment (FGS) was only found in H5N1 rather than any other subtype. This FGS is a 30-bp gene segment mainly consisting of ‘A’ and ‘G’. When translated into amino acids the FGS converted into a sequence of mainly basic amino acids with positive charges. This feature amino acid segment (FAAS) was located in the cleavage site loop of HA which was potentially cleavable by various proteases. The 3D structure of H5N1 HA was reconstructed using homology modelling. It was found that the cleavage site loop was well exposed to potential proteases. The molecular surfaces were reconstructed to study how mutation and deletion of some amino acids in the FAAS affected the charge distribution. It was found that some mutations had severely changed the landscape of the charge dis- tribution. Statistical analyses of FAAS were made with respect to when and where the H5N1 viruses were found. In 2005, there were less un-mutated FAAS than the other years according to temporal evolution, and more mutated FAAS appeared in China than other regions according to geographic dis- tribution. These results are helpful for exploring the evolution of virus high pathogenicity.展开更多
文摘The emulation of characteristics of a different organism to gain biological advantage is a common phenomenon in nature,described and defined with the term"mimicry"in the second half of the 19th century.In the last decades,mimicry at molecular level has been evidenced as a method used by several pathogen microrganisms to control metabolic functions of infected cells and elude host’s immune system.Because of molecular mimicry,immune reactions against microbial molecules can turn against the mimicked self-molecules in predisposed subjects,leading to autoimmunity.This pathogenic mechanism,which gives a possible explanation for the specific epidemiological and chronological association between some infections and some autoimmune diseases,is well known and verified in many fields of medicine,but not adequately studied in dermatology:experimental data are available only for leprosy,atopic dermatitis,Beh?et’s disease,Vogt-Koyanagi-Harada syndrome and systemic erythematous lupus,while for few other diseases its role is hypothetical or suggested on the basis of single,small experiments or anecdotal reports.An overview of available data and hypotheses about the role of molecular mimicry in autoimmune cutaneous diseases is presented here,together with the perspectives offered by the use of bioinformatics and the personal experi-ence of the author in this field.
基金Supported by the Chinese National Key Research Program of Basic Sciences (Grant No. 2005CB724303)the National Natural Science Foundation of China (Grant No. 10376024)the Tianjin Commission of Sciences and Technology (Grant No. 033801911)
文摘The cleavability of the hemagglutinin (HA) plays a major role in virulence of avian influenza viruses. Detailed analyses of the cleavage sequences and their evolution would give insights into the high pathogenicity of the H5N1 virus. HA segments were visually identifiable in the cellular automata (CA) image, and a feature gene segment (FGS) was only found in H5N1 rather than any other subtype. This FGS is a 30-bp gene segment mainly consisting of ‘A’ and ‘G’. When translated into amino acids the FGS converted into a sequence of mainly basic amino acids with positive charges. This feature amino acid segment (FAAS) was located in the cleavage site loop of HA which was potentially cleavable by various proteases. The 3D structure of H5N1 HA was reconstructed using homology modelling. It was found that the cleavage site loop was well exposed to potential proteases. The molecular surfaces were reconstructed to study how mutation and deletion of some amino acids in the FAAS affected the charge distribution. It was found that some mutations had severely changed the landscape of the charge dis- tribution. Statistical analyses of FAAS were made with respect to when and where the H5N1 viruses were found. In 2005, there were less un-mutated FAAS than the other years according to temporal evolution, and more mutated FAAS appeared in China than other regions according to geographic dis- tribution. These results are helpful for exploring the evolution of virus high pathogenicity.
