Pesquisa afirma que o HIV evolui rápido para driblar resposta imunológica
Vírus HIV
Um estudo [Adaptation of HIV-1 to human leukocyte antigen class I ] envolvendo cientistas de vários países demonstrou que o vírus da Aids, HIV, está evoluindo rapidamente para driblar respostas imunológicas do organismo.
O trabalho, publicado pela revista científica Nature, sugere que, como acontece com o vírus da gripe, eventuais vacinas contra o HIV terão de ser constantemente atualizadas. Da BBC Brasil, com informações complementares do EcoDebate
Os pesquisadores demonstraram que o HIV é capaz de se adaptar rapidamente para neutralizar moléculas do sistema imunológico controladas por genes conhecidos como Antígenos de Histocompatibilidade Humana (Human Leucocyte Antigen, HLA, na sigla em inglês).
O vírus já matou 25 milhões de pessoas no mundo e outras 33 milhões estão infectadas.
Mas o HIV não mata as pessoas com a mesma rapidez. Em média, sem tratamento, uma pessoa vive com o vírus durante dez anos antes de desenvolver a Aids.
Algumas desenvolvem a doença após 12 meses e outras após 20 anos.
O progresso da infecção está vinculado ao gene HLA, que controla a produção de importantes moléculas do sistema imunológico.
Seres humanos possuem quantidades diferentes do gene HLA e, mesmo variações mínimas, podem ter grande impacto sobre quão rapidamente a Aids se desenvolverá.
Os pesquisadores examinaram sequências genéticas do HIV e genes HLA em mais de 2.800 pacientes em vários países, entre eles, Grã-Bretanha, Austrália, África do Sul, Canadá e Japão.
Eles constataram que mutações que permitem que o HIV neutralize o efeito de um determinado gene HLA são mais frequentes em populações onde há grande incidência desse gene específico.
Por exemplo, uma forma do gene HLA chamada B*51 é particularmente efetiva em controlar o HIV – a menos que o vírus esteja equipado com uma mutação genética “de escape”.
Japão
Em seus estudos, os pesquisadores constataram que, no Japão, onde o gene B*51 é bastante comum, dois terços da população infectada é portadora de uma variante do HIV equipada com a mutação.
Na Grã-Bretanha, por outro lado, onde o gene é muito menos comum, entre 15 e 25% dos pacientes são portadores do HIV que sofreu a mutação.
O responsável pelo estudo, Philip Goulder, da Universidade de Oxford, disse que resultados semelhantes foram vistos em cada tipo de gene HLA estudado.
“Isto mostra que o HIV é extremamente ágil em se adaptar às respostas imunológicas das populações”, disse Goulder.
“Isto é evolução em alta velocidade que estamos vendo em um período de apenas duas décadas”.
“A tentação é achar que isso é uma má notícia, que esses resultados significam que o vírus está ganhando a batalha”.
“Não é necessariamente o caso. Pode ser que, da mesma forma, à medida em que o vírus muda, respostas imunológicas diferentes entrem em ação e sejam mais efetivas”.
“A implicação é que, uma vez que tenhamos descoberto uma vacina efetiva, ela tenha de ser alterada frequentemente para acompanhar o vírus em evolução, assim como fazemos hoje com a vacina da gripe.”
* Matéria da BBC Brasil,Atualizado em 26 de fevereiro, 2009 – 11:28 (Brasília) 14:28 GMT
O artigo “Adaptation of HIV-1 to human leukocyte antigen class I”, publicado na revista Nature, (25 Feb 2009), doi: 10.1038/nature07746, Letters to Editor, apenas está disponível para assinantes. Abaixo transcrevemos o abstract e o release da University of Oxford.
Adaptation of HIV-1 to human leukocyte antigen class I
Yuka Kawashima, Katja Pfafferott, John Frater, Philippa Matthews, Rebecca Payne, Marylyn Addo, Hiroyuki Gatanaga, Mamoru Fujiwara, Atsuko Hachiya, Hirokazu Koizumi, Nozomi Kuse, Shinichi Oka, Anna Duda, Andrew Prendergast, Hayley Crawford, Alasdair Leslie, Zabrina Brumme, Chanson Brumme, Todd Allen, Christian Brander, Richard Kaslow, James Tang, Eric Hunter, Susan Allen, Joseph Mulenga, Songee Branch, Tim Roach, Mina John, Simon Mallal, Anthony Ogwu, Roger Shapiro, Julia G. Prado, Sarah Fidler, Jonathan Weber, Oliver G. Pybus, Paul Klenerman, Thumbi Ndung’u, Rodney Phillips, David Heckerman, P. Richard Harrigan, Bruce D. Walker, Masafumi Takiguchi, Philip Goulder
The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host–pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8+ T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection1. Mutation within these epitopes can allow viral escape from CD8+ T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128–135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8+ T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.
HIV is evolving to evade human immune responses
HIV is evolving rapidly to escape the human immune system, an international study led by Oxford University has shown. The findings, published in Nature, demonstrate the challenge involved in developing a vaccine for HIV that keeps pace with the changing nature of the virus.
‘The extent of the global HIV epidemic gives us a unique opportunity to examine in detail the evolutionary struggle being played out in front of us between an important virus and humans,’ says lead researcher Professor Philip Goulder of the Peter Medawar Building for Pathogen Research at Oxford University.
‘Even in the short time that HIV has been in the human population, it is doing an effective job of evading our best efforts at natural immune control of the virus. This is high-speed evolution that we’re seeing in the space of just a couple of decades.’
HIV has already killed 25 million people, and an estimated 33 million are currently infected. However, HIV does not kill all people at the same rate. On average, an adult with HIV will survive for ten years without anti-HIV drugs before developing AIDS. But some people will progress to AIDS within 12 months while others can make effective immune responses to the virus and survive without any anti-HIV therapy for over 20 years.
Genes encoding a key set of molecules in the human immune system called the human leucocyte antigens (HLA) are critically important. HLA determine the progress of many infectious diseases including HIV, and enable the recognition and killing of HIV-infected cells. Humans differ from each other in the exact HLA genes they have, and small differences can make the difference in how long it takes to progress to AIDS.
The extent of the global HIV epidemic gives us a unique opportunity to examine in detail the evolutionary struggle being played out in front of us between an important virus and humans.
Professor Philip Goulder
The research team set out to determine whether HIV is adapting to human immune responses. They looked at HIV genetic sequences in different countries around the world, including the UK, South Africa, Botswana, Australia, Canada, and Japan, wanting to see whether the HIV sequences could be related to the different HLA genes present in the different populations.
The collaboration between Oxford University, the Ragon Institute at Massachusetts General Hospital, Kumamoto University in Japan, the Royal Perth Hospital and Murdoch University in Australia and others analysed the genetic sequences of the HIV virus and human leucocyte antigen (HLA) genes in over 2,800 people. The work was funded by a number of organisations including the Wellcome Trust, the Medical Research Council, the US National Institutes of Health, and Oxford’s James Martin 21st Century School.
Mutations that allow HIV to get round immune responses directed by a particular HLA gene were found more frequently in populations with a high prevalence of that HLA gene. This is strong evidence for HIV adaptation to the human immune system at the level of populations.
‘Where a favourable HLA gene is present at high levels in a given population, we see high levels of the mutations that enable HIV to resist this particular gene effect,’ says author Professor Rodney Phillips, co-director of the James Martin Institute for Emerging Infections at Oxford University. ‘The virus is outrunning human variation, you might say.’
‘The temptation is to see this as bad news, that these results mean the virus is winning the battle,’ says Professor Goulder. ‘That’s not necessarily the case. It could equally be that as the virus changes, different immune responses come into play and are actually more effective.’
The results are important because it is our most effective immune responses that vaccines against HIV would try and boost to a level that would protect against the virus.
‘The implication is that once we have found an effective vaccine, it would need to be changed on a frequent basis to catch up with the evolving virus, much like we do today with the flu vaccine,’ explains Professor Goulder.
‘In this anniversary year of Darwin’s birth, we are accustomed to think of evolution happening over thousands, tens of thousands and even millions of years,’ says Professor Goulder. ‘But we are seeing changes in HIV, and our immune response to the virus, in just a couple of decades.’
[EcoDebate, 28/02/2009]
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