Research On Evolutionary Of Rabies Virus Quasispecies Adaptation

Rabies is a serious zoonosis which presents a significant public health risk in most parts of the developing world.It causes brain and central nervous system damage.Once symptoms of rabies develop,it is 100% fatal to both infected animals and human.There are 55,000 deaths reported annually,most of them were in the developing world,especially in Asia and Africa.The morbidity and mortality of China is second only to India of the world.Because of the fatal affection and wide range of hosts,rabies becomes hard to prevent and control.Great efforts had been done in controlling human Rabies in many developed countries,but it is very difficult to control Rabies well.So it is essential to study the characteristics of rabies.If we know deeply and carefully on the Rabies and Rabies related virus(RV),it has the benefit of rabies prevention.The host of rabies virus are extensive,including almost all of the warm-blooded mammalian species.The concept of quasispecies of RNA virus provide a new point of view of understanding rabies virus,it can make the spread of virus more easily.So,it is necessary to do research on rabies virus quasispecies.In order to study the spread of rabies virus street strain in the new host and its variation in the process of adapting to the new host,we first selected five strains(Hu ND03,SXLF03,FJ02,CQQJD09,927A)and the fixed strain CVS-11,the mice infected with the virus were killed and the animal brain tissue was inoculated into the brain,which was F1,which was transmitted to the 15 th generation at the neonatal level.The primordial brain tissues of F2,F7,F10,F15 generation mouse and Hu ND03,SXLF03,FJ02,CQQJD09,927 A were obtained from Hu ND03,SXLF03,FJ02,FQ02,CQQJD09,927 A,respectively,and the rabies virus G gene full length sequence.The amplified samples were sequenced using the Illumina Hiseq 2500 sequencing method and analyzed by multiple sequences.Results showed that nucleotide mutations were found in the G gene sequences of 302,and quasispecies present in these three RABV isolates.Our results only found point mutants in the mutant form of viral quasispecies,no deletion mutant,insertion mutants,termination mutants were seen.The mostfrequent mutants found was T→C and A→G.In addition,the quasispecies complexity is different in various isolates and inter-generations of the same isolate..There were two different kinds of mechanism inthese quasispecies to fit under the pressures that come from the infection host change:competence and elimination.The distribution of the mutations observed in G gene concentrated ectodomain,followed by endodomain,transmembrane domain and signal peptide domain.And there were a few mutants concentrated in antigen sites of Hu ND03,the mutants of CQQJD09 concentrated in glycosylation sites and pathogenicity sites.These results suggest that quasispecies occurred in different generations of various isolates is related to the adaptation of RABV isolates to the new host,while the length of this process is dependent on the evolutionary position of the selected isolates.Overall,this study primarily illustrates the quasispecies complexity of RABV street isolates and the dynamics of them in the adaptation process to the new host.Thus,this research provides important insights into elucidating the relationship between RABV quasispecies and its widest host range,and exploring the molecular mechanism of cross-species transmission of RABV.