The Natural Selection of HIV

During the asymptomatic period of HIV infection, the numbers of HIV virus particles in an infected person's bloodstream is relatively low. However, the immune response to HIV does not completely eliminate the virus. HIV persists inside immune-system structures called lymph nodes where it continues to infect and kill T4 cells. The dying T4 cells release the virus into the bloodstream, where anti-HIV antibodies quickly eliminate them. At the same time, the infected individual is maintaining a high rate of T4 cell production to replace those lost to HIV. In a sense, the virus and the immune system maintain a balance of power during this period.

The population of HIV is not stable during the asymptomatic period, however. HIV particles are constantly being reproduced because they continue to infect cells in the lymph nodes; any time there is reproduction, mutation can occur. As a result, during the asymptomatic period new variants of HIV arise. Some of these HIV variants have mutated antigens. The change in antigens can be great enough that the antibodies that attacked the HIV particles produced early in the infection do not recognize the new variants. Thus, these new variants have higher fitness than the older variants as a result of their longer survival in the bloodstream. As the new HIV antigen variant becomes more common, the host's immune system develops an antibody to it, and HIV again begins to be cleared from the bloodstream—until the next new antigen variant arises through mutation. In other words, the population of HIV inside the host is continually evolving, and the host's immune system is continually trying to "catch up" (Figure 9.11).

Among viruses, HIV has an unusually high rate of mutation. Some scientists estimate that every single HIV particle produced has at least one difference from the HIV it arose from. In addition, HIV has an enormously high rate of replication. These two characteristics of HIV result in a population of virus within an asymptomatic host that contains on the order of one billion distinct variants.

HIV's rapid evolution appears to cause the eventual end of the asymptomatic period in an infected person. The immune system is able to produce antibodies to many different HIV antigen variants, but eventually the sheer number of different variants of HIV that the immune system must respond to becomes overwhelming. Finally, one variant arises that escapes immune-system control for a long period, large numbers of T4 cells become infected, and the infected individual becomes increasingly immune deficient. This change initiates the onset of AIDS. The relentless evolution of HIV within an infected person's body eventually exhausts his or her ability to control this deadly virus.

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