Dynamic Immune Responses Maintain Cytotoxic T Lymphocyte Epitope Mutations in Transmitted Simian Immunodeficiency Virus Variants

(Nature Immunol. 6, 247-252, 2005)

Speaker: Yu-wen Chen                                        Room: 601

Commentator: Ih-Jen Su                                      Time: 2005/04/13 PM 1:10~2:00

Abstract:

       People infected by human immunodeficiency virus (HIV) will have acquired immune deficiency and finally be dead with multiple infectious diseases. To investigate problems of HIV infection, simian immunodeficiency virus (SIV) infecting rhesus monkey was often taken as an animal model. In previous study, people found that cytotoxic T lymphocyte (CTL) - based DNA vaccine of SIVsmE660 was eventually failed because of virus CTL epitope mutation. One of the major CTL epitope mutant sites was at Gagp11C (a.a. 181-189) ^2,3. The authors in this paper like to assess the stability of viral mutations in CTL epitope after transmission to naïve hosts. After inoculating the virus variants with mutations on Gagp11C to naïve rhesus monkeys, a dynamic CTL response to Gag protein, but not Env or Pol protein, was enhanced in MHC-matched  (Mamu-A*01-positive) monkeys. Further assessing the amino acid sequence at Gagp11C, they found that virus would transient reverse to wild type sequence in the MHC-matched  (Mamu-A*01-positive) monkeys but permanent reverse to wild type sequence in the MHC-mismatched (Mamu-A*01-negative) monkeys. Overall, the dynamic CTL response could maintain transmitted SIV CTL-epitope mutations; the phenomena might apply to HIV. It can be speculated that CTL-based AIDS vaccine may facilitate the emergence of viruses with CTL-epitope mutation by increasing immunological selection pressure on dominant epitopes after infection. The virus may spread and accumulate on a population depending on the MHC heterogenicity of the population.

References

1.      Barouch, D. H. et al. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocyte. Nature 415, 335-339(2002).

2.      Barouch, D. H. et al. Viral escape from dominant SIV epitope-specific CTL in DNA vaccinated rhesus monkeys. J. virol. 77, 7367-7375(2003).