Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution.
It has been suggested that HIV-1 has evolved its set-point virus load to be optimized for transmission. Previous epidemiological models and studies into the heritability of set-point virus load confirm that this mode of adaptation within the human population is feasible. However, during the many cyc...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-12-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC4270429?pdf=render |
| _version_ | 1818056956960571392 |
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| author | Christiaan H van Dorp Michiel van Boven Rob J de Boer |
| author_facet | Christiaan H van Dorp Michiel van Boven Rob J de Boer |
| author_sort | Christiaan H van Dorp |
| collection | DOAJ |
| description | It has been suggested that HIV-1 has evolved its set-point virus load to be optimized for transmission. Previous epidemiological models and studies into the heritability of set-point virus load confirm that this mode of adaptation within the human population is feasible. However, during the many cycles of replication between infection of a host and transmission to the next host, HIV-1 is under selection for escape from immune responses, and not transmission. Here we investigate with computational and mathematical models how these two levels of selection, within-host and between-host, are intertwined. We find that when the rate of immune escape is comparable to what has been observed in patients, immune selection within hosts is dominant over selection for transmission. Surprisingly, we do find high values for set-point virus load heritability, and argue that high heritability estimates can be caused by the 'footprints' left by differing hosts' immune systems on the virus. |
| first_indexed | 2024-12-10T12:37:05Z |
| format | Article |
| id | doaj.art-efae74bcb4534e9ebe3869e9988cc886 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-10T12:37:05Z |
| publishDate | 2014-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-efae74bcb4534e9ebe3869e9988cc8862022-12-22T01:48:37ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582014-12-011012e100389910.1371/journal.pcbi.1003899Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution.Christiaan H van DorpMichiel van BovenRob J de BoerIt has been suggested that HIV-1 has evolved its set-point virus load to be optimized for transmission. Previous epidemiological models and studies into the heritability of set-point virus load confirm that this mode of adaptation within the human population is feasible. However, during the many cycles of replication between infection of a host and transmission to the next host, HIV-1 is under selection for escape from immune responses, and not transmission. Here we investigate with computational and mathematical models how these two levels of selection, within-host and between-host, are intertwined. We find that when the rate of immune escape is comparable to what has been observed in patients, immune selection within hosts is dominant over selection for transmission. Surprisingly, we do find high values for set-point virus load heritability, and argue that high heritability estimates can be caused by the 'footprints' left by differing hosts' immune systems on the virus.http://europepmc.org/articles/PMC4270429?pdf=render |
| spellingShingle | Christiaan H van Dorp Michiel van Boven Rob J de Boer Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution. PLoS Computational Biology |
| title | Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution. |
| title_full | Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution. |
| title_fullStr | Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution. |
| title_full_unstemmed | Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution. |
| title_short | Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution. |
| title_sort | immuno epidemiological modeling of hiv 1 predicts high heritability of the set point virus load while selection for ctl escape dominates virulence evolution |
| url | http://europepmc.org/articles/PMC4270429?pdf=render |
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