Nós respondemos a infecções em duas formas fundamentais. Um delas é ‘resistência’, onde o corpo ataca o patógeno invasor e reduz os seus números. Outra, que é muito menos bem compreendida, é “tolerância”, onde o corpo tenta minimizar os danos causados pelo patógeno. Um estudo utilizando dados de um grande grupo suíço de indivíduos infectados pelo HIV gives us a glimpse into why some people deal with HIV better than others.
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.
O HIV oferece uma oportunidade única para desmembrar a maneira que o corpo humano lida com a doença. Após o evento inicial da infecção, o vírus passa a residir em uma população de glóbulos brancos chamados linfócitos T CD4 +. O número de vírus, alguns meses após a infecção, chamado de “carga viral set-point”, pode ser usado para medir a resistência – o quão bem uma pessoa está lutando contra o vírus. No entanto, a infecção pelo HIV também oferece uma medida imediata de tolerância – quanto mais lento você perder suas células T CD4 +, melhor você está tolerando a infecção. Esta situação de convivência entre o ser humano e o vírus pode durar muitos anos, mas quando o número de células T CD4 + desce abaixo de um nível crítico (menos de 200 células por microlitro de sangue), o sistema imunitário fica comprometido e o portador de HIV torna-se um paciente com AIDS , with potentially fatal consequences if not properly addressed.
The key to the study is the existence of the Swiss HIV cohort study, which started in 1988, - which provided the authors with more than 3000 HIV-infected people who could measure both viral load setpoint and CD4 + T rate and CD4 cell loss. These two values could be used to simultaneously assess resistance and tolerance, and by combining them with a wealth of demographic and genetic data on the same individuals, allowed the authors to begin exploring the functioning of tolerance.
The first question they asked was age and about sex. On average, they found, men and women tolerated HIV equally equally, but older people had a lower tolerance, with the disease progressing almost twice as fast in one with 60 years of age, relative to one of 20's age.
The authors then looked at hereditary factors that influence HIV tolerance. They looked at the genetic differences that are known to be associated with HIV resistance and asked if they were also associated with tolerance. The answer was an overwhelming "no," confirming the expectation that 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 in this cohort of people with HIV, tolerance and resistance could be independent or go hand in hand.
The authors state that “these findings add to our understanding of how“ hosts ”tolerated infections and could open new avenues for treating infections.” The most exciting thing about tolerance is that - as opposed to resistance - it is expected to be “evolution-proof.” One of the problems with gaining resistance to a virus, either naturally or using drugs, is that it is in the virus's interest to develop evasive tactics that circumvent the resistance mechanism. However, the tolerance of the virus is such that viral evolution of the human host 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