In:
eLife, eLife Sciences Publications, Ltd, Vol. 7 ( 2018-03-20)
Abstract:
The HIVvirus infects cells of the immune system. Once inside, it hijacks the cellular molecular machineries to make more copies of itself, which are then transmitted to new host cells. HIV eventually kills most cells it infects, either in the steps leading to the infection of the cell, or after the cell is already producing virus. HIV can spread between cells in two ways, known as cell-free or cell-to-cell. In the first, individual viruses are released from infected cells and move randomly through the body in the hope of finding new cells to infect. In the second, infected cells interact directly with uninfected cells. The second method is often much more successful at infecting new cells since they are exposed to multiple virus particles. HIV infections can be controlled by using combinations of antiretroviral drugs, such as efavirenz, to prevent the virus from making more of itself. With a high enough dose, the drugs can in theory completely stop HIV infections, unless the virus becomes resistant to treatment. However, some patients continue to use these drugs even after the virus they are infected with develops resistance. It is not clear what effect taking ineffective, or partially effective, drugs has on how HIV progresses. Using efavirenz, Jackson, Hunter et al. partially limited the spread of HIV between human cells grown in the laboratory. The experiments mirrored the situation where a partially resistant HIV strain spreads through the body. The results show that the success of cell-free infection is reduced as drug dose increases. Yet paradoxically, in cell-to-cell infection, the presence of drug caused more cells to become infected. This can be explained by the fact that, in cell-to-cell spread, each cell is exposed to multiple copies of the virus. The drug dose reduced the number of viral copies per cell without stopping the virus from infecting completely. The reduced number of viral copies per cell made it more likely that infected cells would survive the infection long enough to produce virus particles themselves. Viruses that can kill cells, such as HIV, must balance the need to make more of themselves against the speed that they kill their host cell to maximize the number of infected cells. If transmission between cells is too effective and too many virus particles are delivered to the new cell, the virus may not manage to infect new hosts before killing the old ones. These findings highlight this delicate balance. They also indicate a potential issue in using drugs to treat partially resistant virus strains. Without care, these treatments could increase the number of infected cells in the body, potentially worsening the effects of living with HIV.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.30134.001
DOI:
10.7554/eLife.30134.002
DOI:
10.7554/eLife.30134.003
DOI:
10.7554/eLife.30134.004
DOI:
10.7554/eLife.30134.005
DOI:
10.7554/eLife.30134.006
DOI:
10.7554/eLife.30134.007
DOI:
10.7554/eLife.30134.008
DOI:
10.7554/eLife.30134.009
DOI:
10.7554/eLife.30134.010
DOI:
10.7554/eLife.30134.011
DOI:
10.7554/eLife.30134.012
DOI:
10.7554/eLife.30134.013
DOI:
10.7554/eLife.30134.014
DOI:
10.7554/eLife.30134.015
DOI:
10.7554/eLife.30134.016
DOI:
10.7554/eLife.30134.017
DOI:
10.7554/eLife.30134.018
DOI:
10.7554/eLife.30134.019
DOI:
10.7554/eLife.30134.020
DOI:
10.7554/eLife.30134.021
DOI:
10.7554/eLife.30134.022
DOI:
10.7554/eLife.30134.023
DOI:
10.7554/eLife.30134.024
DOI:
10.7554/eLife.30134.025
DOI:
10.7554/eLife.30134.026
DOI:
10.7554/eLife.30134.027
DOI:
10.7554/eLife.30134.028
DOI:
10.7554/eLife.30134.029
DOI:
10.7554/eLife.30134.030
DOI:
10.7554/eLife.30134.031
DOI:
10.7554/eLife.30134.032
DOI:
10.7554/eLife.30134.033
DOI:
10.7554/eLife.30134.034
DOI:
10.7554/eLife.30134.035
DOI:
10.7554/eLife.30134.039
DOI:
10.7554/eLife.30134.040
DOI:
10.7554/eLife.30134.037
DOI:
10.7554/eLife.30134.038
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2018
detail.hit.zdb_id:
2687154-3
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