Investigation Of Epidemic Characteristics And Viral Gene Function Of Recombinant Strain HIV-1 CRF07_BC Based On Full-length Genome

As one of the dominant circulating strains in China,HIV-1 CRF07_BC recombinant strain is transmitted very rapidly across the country.It is necessary and urgent to identify the virological properties and genomic characteristics of the currently circulating recombinant strain.This study will focus on the genomic characteristics of the recombinant strains in the main pandemic regions—Sichuan and Xinjiang provinces,as well as the virus transmission linkage among different epidemic regions.Moreover,the study will also introduce a strategy for the construction of an infectious clone and its application in viral biology research.Compared to four earlier genome sequences,remarkable gene variation was found in the genome of the currently circulating CRF07_BC,especially for genes env and nef.Some CRF07_BC subtype specific mutation patterns or conserved epitopes were also found in all CRF07_BC isolates.Phylogenetic and statistical analysis of the genetic distance showed that two different ancestral strains triggered the CRF07_BC epidemic at an early phase. Sichuan-Urumqi early strain group displayed displayed a higher gene homology with currently circulating strains of Sichuan,Gansu and Xinjiang than did Yunnan-Guangxi early strain group.Among the genetic distance of other strain Groups away the early strains Group, the Gansu Group was the smallest one,while the Yili(Xinjiang province) Group were the farthest one.Furthermore,very high gene homology(95%) and close epidemic linkage were found among current isolates from Sichuan,Xinjiang and Gansu.The 7 amino acids deletion in Gag P6 protein was a CRF07_BC-related subtype-specific mutation and may be the predominant transmission genotype,owing to its high prevalence in infectious population.Phylogenetic analysis suggested that deletion-genotype strains originated from non-deletion genotype strains and that several ancestral strains exit simultaneously.The 7 aa deletion leads to a remarkable change of secondary and tertiary structures of the P6 protein,which may have effects on fitness and disease progression of deletion-genotype strains in the host.Available LTRs and a feasible strategy are important for the construction of an infectious clonse.Chimeric clone strategy has proved to be successful in rescuing CRF07_BC proviral genome,which was a straightforward,feasible and highly efficent method.Multiple site-directed gene mutation leads to different effects of attenuated chimeric clones in vitro:a mutation of Gp41 improves the replication capacity,and mutation of Vpr led to a poor viral titre of the infectious clone.This study filled in a blank spot in domestic research about the genome and the infectious clone of CRF07_BC.Extended knowledge of viral gene evolution and virus transmission linkage provided valuable information in the war against the pandemic.A simple, high performance strategy for the construction of infectious clones provided a powerful tool for investigation of viral biological properties of the recombinant strain.Due to the poor infectious activity of the chimerical clone,this simple and plausible strategy still requires much improvement.