December 1: Gamma herpesviruses (known as Epstein Barr Virus (EBV) and Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)) are known to be responsible for causing malignancies and mortality in immunosuppressed individuals such as the AIDS patients, especially those with multiple ongoing infections.
Now scientists at Mohali based IISER have discovered a new mechanism that may be targeted to boost immunity against infections and probably some cancers caused by these Gamma herpesviruses.
How this mechanism was identified
In the latest study, researchers generated virus-specific killer T cells (a type of white blood cell which can kill infected cells) having an ability to respond to the Gamma herpesviruses by somatic cell nuclear transplantation (SCNT) approach. This is the same approach by which the sheep “Dolly” was generated. In order to understand how the function and magnitude of virus-specific killer T cells is regulated, scientists compared the expression of genes in virus reactive killer T cells and their genetically comparable counterparts not exposed to the virus.
Scientists found that virus-specific killer T cells expressed a high amount of galectin-3 (an immunoregulatory molecule). On further analysis they found this molecule to be constraining the activation of killer T cell.
Researchers hypothesized that if the function of lgals-3 gene can be disrupted, they could stimulate the immune response to achieve a better virus control.
Importance of this mechanism
According to the scientists, this mechanism could be functional in limiting anti-influenza virus immunity as well as compromising immunological memory that is aimed at protecting individuals later in their lives.
“We are now investigating whether the function of galectin-3 can be disrupted within the virus-specific T cells to enhance their function.”, said Dr. Sharvan Sehrawat.
Research team is now aiming to obtain small molecules to disrupt galectin-3 function in killer T cells from Pharmaceutical companies and have also initiated their own efforts to generate intrabodies indigenously.
“We are optimistic that our future research would yield results that could have translational value and be favourably considered by caregivers engaged in human and animal health care to manage or alleviate sufferings induced by many such infections and cancers”, added Dr. Sharvan.
This whole research work was primarily conducted by a graduate student Manpreet Kaur along with other students Dhanseshwar Kumar and Sudhakar Singh under the guidance of Dr Sharvan Sehrawat at IISER Mohali. The research team also included collaborators Alexandre Esteban, Gerald R.Fink and Hidde L.Ploegh from Boston Children’s Hospital, USA.