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28 Genotype and Phenotype Studies on B/C Recombinant HIV-1 Strain: A Basis for AIDS Vaccine Study in China
Y. Shao*, B. Lu , H. Xing , Q. Zhao , L. Pei, Y. Geng, and P. Pan
Natl. Ctr. for AIDS Prevention and Control, Chinese Academy for Preventive Med., China
Background: Based on the nationwide molecular epidemiology study, Thai-B (B) and recombinant B/C strains were found to be the most prevalent strains in China. To provide the basis for HIV vaccine development in China, it is important to understand the genetic and biological characteristics of the local circulating strains. This study is designed to investigate the relations between the genetic variation and the infection features of the recombinant B/C strain.
Methods: HIV genes of the B/C recombinant strain were obtained by PCR amplification and analyzed by DNA sequencing. In vitro virus culture and serum viral load detection were performed to monitor virus phenotype in the infected host. Genetic mutations were monitored correlated with its phenotype features in a function analysis system.
Results: The recombinant strain has the backbone of C with several insertions of B sequences. The recombinant has less genetic diversity compared with C and B strains. Among isolates, the clade C and B/C recombinants show only NSI and CCR-5 phenotypes, whereas the B has additional SI and CXCR-4 phenotypes. The IDUs infected by the recombinants have a significantly lower viral load compared with either B or C strains. One possible explanation was the specific mutations in the tat protein of the recombinant strains, which further subdivided based on 1 amino acid difference in tat into very low, medium low, and low viral load. The 3 tat genes were cloned and expressed. The functions of the tat mutants were tested in a micro-transfection system containing a luciferase gene under the control of HIV LTR. High, medium, and low Luc activities were induced in a good accordance with the 3 levels of viral load caused by them in vivo.
Conclusions: The circulating recombinant HIV-1 strains predominant in Northwest China have some unique genetic variations and biological characteristics. The low viral load induced by the recombinant strain suggested that a host-adapted feature might exist in this strain. Further studies are needed to investigate their impact on the future epidemic and to provide more information for the candidate vaccine development in China.
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