AEGiS-15IAC: Primary and tertiary structure prediction of EIAV attenuated vaccine and the suggestions for HIV vaccine design.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Primary and tertiary structure prediction of EIAV attenuated vaccine and the suggestions for HIV vaccine design.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10170)

Li HG, Zhang XY, Shao YM
Chinese National Center for HIV/STD prevention and control, Beijing, China

BACKGROUND: Equine Infectious Anemia virus (EIAV), like HIV, belongs to the Lentivirus genus, they are similar not only in morphology, genomic structure, and antigenicity, but also in its replicative and infectious characteristics. In the 1970s, Chinese scientists successfully developed a donkey leukocyte adapted attenuated vaccine, the only lentivirus vaccine developed and applied on a large-scale worldwide. Exploring characteristics of EIAV vaccine will help to design new HIV vaccine.

METHODS: We used JACKAL software package to build three-dimensional structure model of EIAV gp90 based on its homology with HIV gp120 at primary sequence level; O software package to study structure difference between EIAV virulent and vaccine strains, and provided several mutation suggestion based on the structure comparison.

RESULTS: Sequencing both EIAV virulent and vaccine strain revealed that they have a number of amino acid mutations. There are 3 mutations at GAG region, 5 mutations at POL region (2 upstream Protease, 2 at dUTPase and 1 at RTase) and 11 mutations at ENV region. By software modeling and simulation, we found that these mutations mainly alter the surface properties including charge distribution and hydrophobicity. All the mutations are divided into three groups (regions) with proximity at three-dimensional structural level: the 1st region (changed surface charge distribution); the 2nd region (changed interaction between two beta-sheet), and the 3rd region (caused the turn 4th packing more tightly).

CONCLUSIONS: EIAV and HIV share high homology at primary and tertiary structure level. We found the structural difference between EIAV virulent and attenuated vaccine strain, which might contribute to the attenuation of EIAV and possibly affect EIAV and target cell interaction. Based on the results, we provided suggestions on genetic mutation to guide new HIV vaccine development. The feasibility of mutation design is under investigation.

Keywords: AEGIS, Infectious Anemia Virus, Equine, Jackals, AIDS Vaccines, HIV, Viral Envelope Proteins, Genes, gag, Genes, pol, SU protein, equine infectious anemia virus, Animal, genetics

040711
A10170