Scientists look for a way to neutralise the HIV threat

Sunday, 1 December, is World AIDS Day. This year, the World Health Organization (WHO) is highlighting the need for broader engagement by community health workers - to strengthen primary care and, in turn, the fight against the HIV epidemic. According to UNAIDS, over 38 million people are living with HIV/AIDS in the world. AIDS or acquired immunodeficiency syndrome is another name for stage 3 human immunodeficiency virus or HIV infection. It occurs when the virus has severely compromised the immune system. [caption id=“attachment_7706471” align=“alignleft” width=“380”]  Representational image. Image source: Getty Images.[/caption] Researchers have been trying to find a cure for AIDS for half-a-century. Now, in a creative leap, they’re looking at a different, but related, virus to find a way to neutralise the HIV threat.

The other virus

Called the Simian Immunodeficiency Virus or SIV, this virus is remarkably similar to HIV. Except in two main respects. One, the species of monkeys that are natural hosts for these viruses. While the African green monkeys naturally acquire SIV, it is the white Rhesus macaque who are prone to get HIV/AIDS. Two, while the African green monkeys can go through life without getting sick, the Rhesus macaque usually die from AIDS-related complications. So, what are the researchers hoping to do here?

The research question

SIV is an HIV-like virus that can infect monkeys and apes and cause a disease similar to AIDS. In fact, researchers sometimes study SIV as a way to learn more about HIV because HIV and SIV are closely-related viruses. The recent research, published in the peer-reviewed journal  Nature Communications, started with a simple question: how do certain monkeys that carry the SIV virus avoid disease progression throughout their lives? Here’s what happens when someone gets HIV infection: the infection affects the T-helper cells (also known as the CD4+ T cells) in the immune system and trashes them. Once this is done, the body is unable to fight off infections like tuberculosis and pneumonia.   Depletion of these CD4+ T cells in the body is usually a sign of the presence of AIDS. That is, in everyone except African green monkeys, who don’t get sick even with millions of SIV viruses coursing through their blood vessels. The researchers found that even in African green monkeys with high levels of viral markers viremia (virus in the blood) and major mucosal CD4+ T cell depletion due to the presence of SIV, these species remained disease-free! Next, the researchers introduced SIV in the body of Asian non-human primates like Rhesus macaques - but these monkeys started showing signs of AIDS, including CD4+ T cell loss, collagen formation in the lymphoid tissue (fibrosis), excessive blood clotting (hypercoagulation), breakdown of the intestinal mucosa, and other infections soon after.

Where does that leave us?

The scientists were keen to find the factors that were protecting these African green monkeys against AIDS. To accomplish this, they did a Conserved Gene Signature Analysis (CGSA) on both African green monkeys and Rhesus macaques with acute SIV infection. The analysis was designed to compare the RNA sequencing of the African green monkeys and Rhesus macaque to various other species. In all mammals, including humans, RNA or ribonucleic acid takes instructions from the DNA to form proteins like hormones and enzymes in the body. For this research, the scientists took RNA from the monkeys’ rectum. Here’s what they found: African green monkeys rapidly activate a regenerative wound healing mechanism in their mucosal tissue. Also, the wound healing protein, fibronectin, showed faster tissue distribution in African green monkeys. In short, they heal super fast. But that wasn’t all. African green monkeys have monocytes (a type of white blood cells) that show repair and regeneration along with a cytokine (immune cells of the body) called transforming growth factor-beta 1 that helps in functions like controlling cell growth, cell proliferation and cell differentiation. The African green monkeys also showed less inflammatory genes as compared to Rhesus macaques.

So what?

HIV virus essentially fries T-helper cells in the immune system of humans as well as many monkeys and apes. The African green monkeys, however, have an exceptional regenerative wound healing process. They can preserve mucosal integrity and prevent inflammation. The researchers were also able to pinpoint some changes in the bodies of African green monkeys, which strengthen their immune system: (1) The sequence of some of their immune cells — CD4 or CCR5 — literally changes to restrict the spread of infection, even when the body’s white blood cell count is down. (Typically, it is the job of white blood cells to fight infection.) (2) African green monkeys are also able to activate their in-built immune system. (3) These monkeys are also able to maintain their mucosal layers - the inner, protective lining of organs. Whereas, this lining is damaged in other species with SIV infection. (4) African green monkeys also have fewer macrophages, a type of white blood cells, in response to SIV/HIV infection.

Future plans

Scientists aim to further understand these changes in African green monkeys, who are immune to SIV, to develop therapies that can prevent inflammatory disease and AIDS.   They also plan to find the immune cells, other than macrophages, that are likely to be involved in regenerative wound healing and which possibly have a protective effect against HIV infection. Health articles in Firstpost are written by myUpchar.com, India’s first and biggest resource for verified medical information. At myUpchar, researchers and journalists work with doctors to bring you information on all things health. For more information, please read our article on   HIV/AIDS_._