Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo.
Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progress...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2006-04-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC1395353?pdf=render |
| _version_ | 1818905548099158016 |
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| author | Becca Asquith Charles T T Edwards Marc Lipsitch Angela R McLean |
| author_facet | Becca Asquith Charles T T Edwards Marc Lipsitch Angela R McLean |
| author_sort | Becca Asquith |
| collection | DOAJ |
| description | Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role. Yet virus clearance rates following antiretroviral therapy are not impaired in individuals with advanced HIV disease, suggesting that weakening of the CTL response is not the major underlying cause of disease progression and that CTLs do not have an important protective role. Here we reconcile these apparently conflicting studies. We estimate the selection pressure exerted by CTL responses that drive the emergence of immune escape variants, thereby directly quantifying the efficiency of HIV-1-specific CTLs in vivo. We estimate that only 2% of productively infected CD4+ cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 10(7)) per day but are not responsible for the majority of infected cell death. |
| first_indexed | 2024-12-19T21:25:05Z |
| format | Article |
| id | doaj.art-e5f5662136b641408f6e3e5cf6c43e72 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-19T21:25:05Z |
| publishDate | 2006-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-e5f5662136b641408f6e3e5cf6c43e722022-12-21T20:05:09ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852006-04-0144e9010.1371/journal.pbio.0040090Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo.Becca AsquithCharles T T EdwardsMarc LipsitchAngela R McLeanUnderstanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role. Yet virus clearance rates following antiretroviral therapy are not impaired in individuals with advanced HIV disease, suggesting that weakening of the CTL response is not the major underlying cause of disease progression and that CTLs do not have an important protective role. Here we reconcile these apparently conflicting studies. We estimate the selection pressure exerted by CTL responses that drive the emergence of immune escape variants, thereby directly quantifying the efficiency of HIV-1-specific CTLs in vivo. We estimate that only 2% of productively infected CD4+ cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 10(7)) per day but are not responsible for the majority of infected cell death.http://europepmc.org/articles/PMC1395353?pdf=render |
| spellingShingle | Becca Asquith Charles T T Edwards Marc Lipsitch Angela R McLean Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. PLoS Biology |
| title | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_full | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_fullStr | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_full_unstemmed | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_short | Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. |
| title_sort | inefficient cytotoxic t lymphocyte mediated killing of hiv 1 infected cells in vivo |
| url | http://europepmc.org/articles/PMC1395353?pdf=render |
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