Related Experiment Videos
A dominant role for CD8+-T-lymphocyte selection in simian immunodeficiency virus sequence variation
David H O'Connor1, Adrian B McDermott, Kendall C Krebs
1Wisconsin Primate Research Center, Department of Pathology, Laboratoty of Medicine, University of Wisconsin, 1300 University Ave., Madison, WI 53706, USA.
Journal of Virology
|November 27, 2004
Summary
CD8(+) T lymphocytes drive viral escape in SIV infections. This immune response is the primary driver of viral diversification outside the envelope, impacting virus evolution.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- CD8(+) T lymphocytes (CD8-TL) are known to select viral escape variants in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections.
- The frequency and impact of CD8-TL-mediated viral escape on overall virus diversification remain largely unquantified.
Purpose of the Study:
- To quantify the extent of CD8-TL selection in SIV infections.
- To determine the contribution of CD8-TL escape to viral diversification outside the viral envelope.
Main Methods:
- Viral genomes were sequenced from 35 SIVmac239-infected animals at the time of euthanasia.
- Analysis focused on positive selection acting on known CD8-TL epitopes and variable loops of the env gene.
- Quantification of viral variation within recognized CD8-TL epitopes.
Main Results:
- Positive selection for sequences encoding 46 known CD8-TL epitopes was comparable to selection on env variable loops.
- >60% of viral variation outside the viral envelope occurred within recognized CD8-TL epitopes.
- CD8-TL selection was identified as the dominant force shaping SIV diversification beyond the envelope.
Conclusions:
- CD8-TL selection significantly contributes to SIV diversification.
- The immune system, specifically CD8-TL, plays a major role in shaping the genetic landscape of SIV outside its envelope.
- Understanding CD8-TL selection is crucial for comprehending SIV evolution and developing therapeutic strategies.