Why some primates can live with HIV without AIDS

Important differences in immune system signaling and the formation of immune-regulating molecules may explain why some primates can live with the immunodeficiency virus that does not reach AIDS. Unlike some other primates, brown monkeys and humans cannot cope with this disease.

As soon as HIV (human immunodeficiency virus) was identified as the cause of AIDS 25 years ago, an extensive study was conducted to understand the origin of the virus. That study led to the discovery that chimpanzees and green-faced monkeys were infected with monkey immunodeficiency virus (SIV) in the wild, then transmitted to humans and brown monkeys causing AIDS. Surprisingly, the natural subject of the AIDS virus, such as the blue-faced monkey and many African primate species infected with SIV in the wild, remains perfectly healthy. The evolution of the natural subject to fight the development of immunodeficiency disease has long been a key mystery without a solution in our understanding of AIDS. In addition, their concept of disease resistance mechanism can help explain the basic mechanism of AIDS development in humans.

A team of scientists at Yerkes National Primate Research Center and the Emory Vaccine Center found that the blue-faced monkey's immune system works at significantly lower levels during SIV infection than The brown monkey's immune system, this difference may explain why SIV and HIV cause AIDS in some species, and do not cause AIDS in some other species.

Mark Feinberg - PhD, doctor and author of the study, said: 'In human HIV infection and SIV in monkeys, the immune system is activated at a high level, increasing destruction. and reduce the formation of essential immune cells, and therefore gradually defeated completely. In contrast, SIV's natural hosts, such as green-faced monkeys, do not exhibit abnormal immune stimulation and do not develop AIDS despite the replication of SIV. Our study explores the basis for very different reactions to AIDS viruses in different primates'. Feiberg was originally an investigator at the Emory Vaccine Center and Yerkes Research Center, and a professor of medicine at Emory Medical University. He is currently the vice president of health and policy for vaccines and infectious diseases at Merck & Co., Inc.

The main cause is a significant difference in immune signals in a type of dendritic cells in the host that is susceptible or resistant to AIDS. Dendritic cells are part of the immune system that plays a role in alerting the body to invading viruses or bacteria, while boosting the immune response to eliminate infection. They detect intruders using molecules called 'toll stations'.

Feinberg's team found that for green-faced macaques, dendritic cells produce less protein interferon alpha (a type of protein that blocks viral growth) - this is an alarm signal to the entire system. immune - when responding to SIV. Therefore, dendritic cells that do not work in the initial stages of SIV infection, and blue-faced monkeys do not produce any significant immune response to the virus. In contrast to blue-faced macaques, dendritic cells in humans and monkeys, subjects that are more susceptible to AIDS, are more likely to be stimulated by HIV and SIV.

Green-faced monkey (Photo: Wikimedia Commons)

Differences in dendritic cell activation for AIDS viruses in some primates are the result of differences in signaling patterns of receptors like the above 'charging stations' . Since most immune responses are unable to eliminate the AIDS virus, replication of the virus leads to the continuous activation of the immune system in humans and monkeys.

Unfortunately, not only can the infection not be destroyed, the stimulation of dendritic cells continuously causes the repeated activation of the immune system and unwanted damage to the immune system in easy species. AIDS. Repeated activation is now recognized as the main cause of AIDS formation.

Green-faced monkey dendritic cells are not easily stimulated by SIV, which may be the reason why blue-faced monkeys do not exhibit excessive immunity and wear AIDS. Therefore, a moderate immune response to SIV in green-faced monkeys may be an effective evolutionary step against the virus whose aggressive anti-viral reactions must be bundled.

The authors stated that a new treatment is needed to prevent the overreaction of the immune system, thereby protecting the body from unwanted damage. Such treatments, focusing on the body's response to the AIDS virus, could be an effective tool to complement drugs that directly suppress the spread of the virus.

Understanding the details of the signaling pathway of the green-faced monkey charging station can be a prerequisite for developing therapies that limit the continuous activation of the immune system in these people infected with HIV.

Feinberf said: 'Understanding the biology of the green-faced monkey and many other primates, the natural host of the AIDS virus, has evolved to resist AIDS is a great lesson for us about pandemics. AIDS, and the death of AIDS in humans. In addition, this valuable knowledge will hopefully help build effective methods for treating HIV. Understanding how SIV's natural hosts are still alive and well can provide new insights into the future evolution of humanity, responding to the extensive pressures in many places around the world, where the consequences of HIV are the most severe. '

The author of the study included Judith N. Mandl of the Graduate Program in Biology, Ecology and Evolution at Emory and Ashley P. Barry universities, who worked at the Emory Vaccine Center and Primate Research Center. national Yerkes.

The study was funded by the National Institutes of Health, with the help of the Emory Vaccine Center and the Yerkes National Primate Research Center.

Refer:
1. Mandl et al.Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections.Nature Medicine, 2008;DOI: 10.1038 / nm.1871