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Viral Replication Capacity as a Correlate of HLA B57/B5801-Associated Nonprogressive HIV-1 Infection
| Content Provider | Scilit |
|---|---|
| Author | Navis, Marjon Schellens, Ingrid van Baarle, Debbie Borghans, José van Swieten, Peter Miedema, Frank Kootstra, Neeltje Schuitemaker, Hanneke |
| Copyright Year | 2007 |
| Description | HLA B57 and the closely related HLA B5801 are over-represented among HIV-1 infected long-term nonprogressors (LTNPs). It has been suggested that this association between HLA B57/5801 and asymptomatic survival is a consequence of strong CTL responses against epitopes in the viral Gag protein. Moreover, CTL escape mutations in Gag would coincide with viral attenuation, resulting in low viral load despite evasion from immune control. In this study we compared HLA B57/5801 HIV-1 infected progressors and LTNPs for sequence variation in four dominant epitopes in Gag and their ability to generate CTL responses against these epitopes and the autologous escape variants. Prevalence and appearance of escape mutations in Gag epitopes and potential compensatory mutations were similar in HLA B57/5801 LTNPs and progressors. Both groups were also indistinguishable in the magnitude of $CD8^{+}$ IFN-γ responses directed against the wild-type or autologous escape mutant Gag epitopes in IFN-γ ELISPOT analysis. Interestingly, HIV-1 variants from HLA B57/5801 LTNPs had much lower replication capacity than the viruses from HLA B57/5801 progressors, which did not correlate with specific mutations in Gag. In conclusion, the different clinical course of HLA B57/5801 LTNPs and progressors was not associated with differences in CTL escape mutations or CTL activity against epitopes in Gag but rather with differences in HIV-1 replication capacity. |
| Ending Page | 3143 |
| Page Count | 11 |
| Starting Page | 3133 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.179.5.3133 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/179/5/3133.full.pdf |
| Journal | The Journal of Immunology |
| Issue Number | 5 |
| Volume Number | 179 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2007-09-01 |
| Access Restriction | Open |
| Subject Keyword | Viral Load Viral Replication Ctl Escape Hla B57/5801 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |