Blocking Protein That Activates Immune Response Found Effective Against HIV Infection

Highlights

• Interferon mediated initial immune response results in prolonged inflammation of CD8 T cells.
• Blocking this interferon 1 allows the CD8 T cells to re-energize and mount a more specific response against HIV.
• The renewed CD8 T cells response and anti-retroviral therapy will lower viral load much more effectively.

An immune response has always been considered necessary in fighting infections, it may no longer be the same, according to scientists from UCLA. It was found that a protein which elicits an immune response should be blocked to help combat HIV, in a study published in the Journal of Clinical Investigation.

Interferon 1

Blocking Interferon 1 could speed up immune response against HIV viral infection and lead to their suppression in individuals who have a chronic infection with HIV and are under anti-viral drug therapy. This is the first study that shows the importance of interferon 1 in the destruction of immune response in HIV positive people.

Senior author of the study, Dr. Scott Kitchen who is an associate professor of medicine in the department of hematology/oncology (David Geffen School of Medicine at UCLA) said, "This finding is completely counterintuitive, because many believe that the more interferon at work, the better. We show that the type of interferon being produced during chronic stages of HIV infection has detrimental effects on the body's ability to fight off HIV and other types of infection or cancer and could actually be contributing to accelerated HIV disease."

HIV Infection

HIV infection leads to an immune response in the body towards the virus in the blood. This immune response that occurs initially is called seroconversion and the infected individual will show signs of illness at this stage and test positive for HIV. After this, the virus will remain in the host body for many years without any apparent effect on the health of the individual. However, the virus, at this stage, would have caused damage to the immune system.

In an immune response to any infection, the CD4 T cells are the first line of defense. These immune cells are also called helper cells as they signal for another type of cells called the CD8 T cells. The HIV virus destroys the CD4 T cells by activating an immune response triggered by Interferon 1. The virus mutates numerous times to evade being detected by the CD8 T cells. The prolonged period of inflammation results in immune exhaustion.

Blocking Interferon 1

The scientists in this study postulated that blocking interferon 1 would not lead to the extended period of inflammation that occurs in an HIV infection. This would let the CD8 T cells recover from the initial attack and will provide time to let them regain in strength.

The scientists believe that the renewed CD8 T cells would be able to mount a more specific response to the virus and these cells, along with the anti-retroviral therapy, will aid in lowering the viral load significantly.

Humanized Mice

The scientists used HIV infected humanized mice -mice that had immune cells, thymus tissue and bone marrow from humans. When the interferon 1 was blocked using antibodies, the immune cells reverted from a state of exhaustion. When the immune cells next mounted an immune response, it was more specifically targeted at the HIV virus and, together with the anti-retroviral therapy, lead to a faster decline in immune cells.

Dr. Kitchen stated that these studies that involved blocking the immune system, resulted in a more potent attack of the virus. The scientists also stated that these experiments were carried out on humanized mice and not on humans, therefore further tests are needed to validate the results.

Dr. Anjie Zhen, a postdoctoral scholar working with UCLA AIDS Institute adds a word of caution when resorting to therapy based on blocking Interferon 1. It could lead to a host of other issues that could occur when the immune function is lowered.

Interferon 1 and CD8 T Cells Response

Interferon 1 was the first interferon to be discovered and this interferon is called 'viral' interferon as they can be induced directly by the virus. The other type of interferon would require specific receptor binding to T cells and natural killer (NK) cells.

The Interferon 1 gets activated by the viral nuclei and proteins. Studies on mice that do not have the interferon 1 have shown that the mice can survive in a pathogen free environment but cannot cope with viral attack.

Type 1 interferon is found to greatly increase the co-stimulatory effect by binding to the IFN1R on the CD8 T cells, greatly increasing their secretion. It has a co-stimulatory effect and drives immune response of T cells. T-cells that are generated late are indirectly sensitized by interferon 1.

The current study, that focuses on suppressing the interferon mediated immune response would aid in blocking the immune response temporarily to provide sufficient time for the CD8 T cells to recover. However, it could make the individual at increased risk for infections, but careful monitoring and care could overcome the reduction in immunity.

References:

1. Anjie Zhen, Valerie Rezek, Cindy Youn, Brianna Lam, Nelson Chang, Jonathan Rick, Mayra Carrillo, Heather Martin, Saro Kasparian, Philip Syed, Nicholas Rice, David G. Brooks, Scott G. Kitchen. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection. Journal of Clinical Investigation, 2016; DOI: 10.1172/JCI89488
2. CD4+ T cell depletion in HIV infection: mechanisms of immunological failure - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729334/)
3. Type 1 Interferons and Antiviral CD8 T-Cell Responses - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252364/)
4. Protein that activates immune response harms body's ability to fight HIV - (https://www.eurekalert.org/pub_releases/2016-12/uoc--pta122216.php)

Source: Medindia