We respond to infections in two fundamental ways. One of them is 'resistance', where the body attacks the invading pathogen and reduces their numbers. Another, which is much less well understood, is "tolerance", where the body tries to minimize the damage caused by the pathogen. A study using data from a large Swiss group of HIV-infected individuals gives us a glimpse as to why some people deal with HIV better than the other.
The authors note that tolerance varies considerably between individuals, which is determined at least in part, by what is inherited genes, and genes that influence the tolerance of HIV are different from those that influence resistance. The team, led by Roland Regoes at ETH Zurich, publishes his work on 16 September in the open access journal PLoS Biology.
HIV provides a unique opportunity to dismember the way the human body copes with the disease. After the initial event of infection, the virus takes up residence in a population of white blood cells called T lymphocytes CD4 +. The number of viruses, a few months after infection, called "viral load set-point" can be used to measure the resistance - how well a person is fighting the virus. However, HIV infection also offers an immediate measure of tolerance - the slower you lose your T CD4 + cells, the better you are tolerating the infection. This situation of coexistence between humans and the virus can last for many years, but when the number of T cells CD4 + falls below a critical level (less than 200 cells per microliter of blood), the immune system is compromised and the carrier HIV becomes an AIDS patient with potentially fatal consequences if not handled properly.
The key to the study is the existence of the Swiss HIV cohort study, started in 1988, - which provided the opportunity to authors with over 3000 HIV-infected persons in whom they could measure both the viral load set point and + T CD4 the rate and loss CD4 cells. These two values could be used to evaluate both resistance and tolerance, and combining them with a wealth of demographic and genetic data on the same individuals, enabled the authors to explore the functioning of tolerance.
The first question they asked was the age and about sex. On average, they found, men and women equally well tolerated HIV, but older people have a lower tolerance to the disease progresses almost two times faster with 60 years of age, compared to a year 20 age.
The authors then looked for hereditary factors that influence tolerance to HIV. They observed genetic differences that are known to be associated with resistance to HIV and asked if they were also associated with tolerance. The response was an overwhelming "no", confirming the expectation that the resistance and tolerance are biologically distinct phenomena.
However, a gene that is involved in resistance also appears to be involved in tolerance. HLA-B gene, which encodes a protein involved in recognition of pathogens by the immune system varies considerably between individuals. Although some of these variants are known to affect a person's resistance to HIV, the authors found other variants of the same gene correlated with tolerance.
So this game key in the immune system appears to influence both tolerance and resistance, but in different ways.
Surprisingly, there seemed to be nothing between tolerance and resistance - this was expected from other studies, but it seemed that this cohort of patients with HIV, tolerance and resistance could be independent or walk side by side.
The authors state that "these findings add to our understanding of how the" hosts The most exciting thing about tolerance is that "tolerated infections and could open new avenues for the treatment of infections." - Unlike resistance - is expected to form to be "the proof of evolution." One of the problems with getting resistance to a virus, either naturally or with the use of drugs is that is in the interest of the virus to develop evasive tactics that circumvent the resistance mechanism. However, the virus tolerance is such that the human host viral evolution should not be a problem.
The work described here represents a first step in exploring the mechanism of tolerance in humans, and once we understand how tolerance works, we might then be in a favorable position to manipulate it and help people living with HIV more comfortably and for longer.
Review: Cláudio Santos de Souza
The above story is based on materials provided by PLoS.
- Roland R. Regoes, Paul J. McLaren, Manuel Battegay, Enos Bernasconi, Alexandra Calmy, Huldrych F. Gunthard, Matthias Hoffmann, Andri Rauch, Amalio Telenti, Jacques Fellay. Dissociate human tolerance and resistance against HIV. PLoS Biology, 2014; 12 (9): e1001951 DOI: 10.1371 / journal.pbio.1001951