When challenged by a pathogen, our body responds in two ways: It puts up a resistance against the pathogen and flushes it out or, if unable to do so, tolerates the pathogen and tries to minimize the damage as much as possible. While resistance is a fairly well-researched field, scientists are still in the dark when it comes to explaining tolerance mechanisms. Now a new study based on tolerance mechanisms in AIDS patients explains why some people cope better with HIV infections than others.

The research, led by Swiss scientist Roland Regoes at ETH Zurich, found that tolerance to HIV varies in individuals and is determined partly by genetics. They also found that genes that influence tolerance are different from those that offer resistance against infections. Their study was published in the online edition of journal PLOS Biology, according to a press release.

When HIV enters the human body, it first attacks the CD4+ T-cells. These cells contain a receptor site to which the virus binds itself. These cells are also the main soldiers of the immune systems, sending out signals to activate the immune system. But when they are attacked by HIV, it impairs their functioning and also that of other crucial cells needed for producing antibodies.

This does not immediately affect the infected person, and he or she may go symptomless for years. This happens because of tolerance. A person’s measure of tolerance against HIV depends on how slowly he or she loses the CD4+ cells. The slower a person loses the cells, the better the disease in being tolerated, until the number of CD4+ cells drops so low that the infection increases and AIDS symptoms appear. Resistance to the infection can be measured a few months after infection by measuring the number of viruses called "set-point viral load” in the body.

The authors based their study on more than 3,000 HIV-infected people, who were part of the Swiss HIV Cohort Study, started in 1988. They measured both the set-point viral load and the rate of CD4+ T-cell loss in these patients. These two values could be used to simultaneously assess both resistance and tolerance. When these values were combined with other genetic data from the patients, the authors could better understand the mechanism of tolerance in individuals.

They found that while sex did not influence tolerance, age did. Older people in general were less tolerant with the disease progressing almost twice as fast in a 60-year-old as in a 20-year-old. They then looked at genetic factors that were thought to contribute to tolerance. They found that genes associated with resistance to HIV were not associated with tolerance, further proving that resistance and tolerance are biologically distinct phenomena.

One gene, however, was found to be an exception and was involved in both resistance and tolerance. This is the HLA-B gene, involved in recognition of pathogens by the immune system. The gene was found to vary considerably between individuals. Although some of these variants are known to influence a person's resistance to HIV, the authors found that other variants of the same gene correlated with tolerance.

So, the authors found that when it comes to HIV, resistance and tolerance could exist independently or work together.

In the long-run, developing tolerance will be quite beneficial, as unlike resistance, tolerance is "evolution proof," according to the authors. This means, though a virus can evolve itself to overcome the host body’s resistance to it, tolerance to a virus is independent of its evolution.

Such studies can provide great insight into manipulating and developing tolerance mechanisms to fight infections like HIV.

Source: Regoes R, McLaren P, Bernasconi E, et al. Disentangling Human Tolerance and Resistance Against HIV. PLOS Biology. 2014.