4.6 Article

Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

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PLOS COMPUTATIONAL BIOLOGY
卷 6, 期 9, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1000906

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资金

  1. U.S. Department of Energy [DE-AC52-06NA25396]
  2. NIH [AI28433, RR06555, P20-RR18754]
  3. Netherlands Organisation for Scientific Research NWO [016.048.603]

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It has recently been estimated that a single HIV-1 infected cell produces between 10(3) and more than 10(4) viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than 10(3) and much smaller than 10(4), individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared.

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