Abstract
It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , 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.
Highlights
The major targets of HIV and simian immunodeficiency virus (SIV) infection are CD4z T cells [1]
In patients chronically infected with HIV-1, more than 10-fold slower clearance rates were found using plasma apheresis to increase viral clearance, and perturb the viral set point [15]
A human cell that is infected with the AIDS virus HIV-1 may produce more than 104 new viral particles over its short life span
Summary
The major targets of HIV and simian immunodeficiency virus (SIV) infection are CD4z T cells [1]. Chronic infection is characterized by a set-point viral load, and rapid turnover of productively infected cells [2,3,4]. To maintain this steady state requires a balance between virus production and clearance, and between target cell production and death. Combining image analysis with in situ hybridization in lymphoid tissue from patients chronically infected with HIV-1, the total number of productively infected CD4z T cells has been estimated to be 108 cells, and the total number of HIV-1 particles has been estimated to exceed 5|1010 virions [5,6]. We shall show below that the situation is more complex
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