Loading...
Please wait, while we are loading the content...
Similar Documents
Dynamics of Immune Escape during HIV/SIV Infection (2008)
| Content Provider | CiteSeerX |
|---|---|
| Author | Althaus, Christian L. Boer, Rob J. De |
| Abstract | Several studies have shown that cytotoxic T lymphocytes (CTLs) play an important role in controlling HIV/SIV infection. Notably, the observation of escape mutants suggests a selective pressure induced by the CTL response. However, it remains difficult to assess the definite role of the cellular immune response. We devise a computational model of HIV/SIV infection having a broad cellular immune response targeting different viral epitopes. The CTL clones are stimulated by viral antigen and interact with the virus population through cytotoxic killing of infected cells. Consequently, the virus population reacts through the acquisition of CTL escape mutations. Our model provides realistic virus dynamics and describes several experimental observations. We postulate that inter-clonal competition and immunodominance may be critical factors determining the sequential emergence of escapes. We show that even though the total killing induced by the CTL response can be high, escape rates against a single CTL clone are often slow and difficult to estimate from infrequent sequence measurements. Finally, our simulations show that a higher degree of immunodominance leads to more frequent escape with a reduced control of viral replication but a substantially impaired replicative capacity of the virus. This result suggests two strategies for vaccine design: Vaccines inducing a broad CTL response should decrease the viral load, whereas vaccines stimulating a narrow but dominant CTL response are likely to induce escape but may dramatically reduce the replicative |
| File Format | |
| Publisher Date | 2008-01-01 |
| Access Restriction | Open |
| Subject Keyword | Hiv Siv Infection Viral Replication Different Viral Epitope Broad Cellular Immune Response Frequent Escape Broad Ctl Response Immune Escape Whereas Vaccine Impaired Replicative Capacity Ctl Clone Viral Load Computational Model Sequential Emergence Realistic Virus Dynamic Inter-clonal Competition Dominant Ctl Response Viral Antigen Single Ctl Clone Ctl Response Cytotoxic Killing Definite Role Several Study Ctl Escape Mutation Escape Mutant Infected Cell Total Killing Cellular Immune Response Virus Population Selective Pressure Several Experimental Observation Vaccine Design Escape Rate Infrequent Sequence Measurement Critical Factor |
| Content Type | Text |
