Université de Montréal
Researchers at the Center hospitalier de l’Université de Montréal (CRCHUM) and Yale University researchers have succeeded in reducing the size of the reservoir where HIV is hiding in humanized mice by using a « can opener ». molecular « and a combination of antibodies found in the blood of infected people.
In its study published in Cell Host & Microbe, the team of scientists, in collaboration with colleagues from the University of Pennsylvania and Harvard University School of Medicine, show that it may also have significantly delayed the return of the virus after the interruption of antiretroviral therapy in this animal model.
Humanized mice are « created » from immunodeficient mice that do not have their own immune system. They have been transplanted with human immune cells and can then be used to study diseases affecting the human immune system, such as cancer, leukemia or HIV. Researchers at Yale University have developed a model of a humanized mouse with active natural killer (NK) cells, a type of immune cell, to examine their role in HIV infection.
“With our cocktail of two antibodies naturally present in the plasma of people infected with HIV and a small ‘can opener’ molecule, we have successfully exposed and stabilized a vulnerable form of the envelope of the virus. This gives time for the antibodies, which recognized the virus, to call the immune system “the police”, the NK cells, and get rid of the infected cells, ”says Andrés Finzi, co-lead author of the study, researcher at CRCHUM and professor at the University of Montreal.
« On our humanized mouse model designed at Yale and used for the study of HIV, we show that the cocktail not only limits the replication of the virus, but also reduces the reservoirs of HIV by destroying the infected cells », explains Priti Kumar, lead author of the study and professor at Yale University.
Throughout the triple therapy, HIV is buried in reservoirs located in the hollow of CD4 + T lymphocytes, white blood cells that help activate the immune system against infections and fight germs.
The existence of these hidden viral sanctuaries explains why antiretroviral therapy cannot cure people with HIV and why they must stay with it throughout their lives in order to keep the virus from « rebounding ».
“In humanized mice, we stopped the triple therapy before administering our cocktail to them. The rebound of the virus took place only 46 days later. In mice that did not receive the cocktail, the rebound occurred within 10 days. Such efficiency in this animal model is really very promising, ”says Andrés Finzi.
These results open up new therapeutic avenues in the fight against this deadly virus. According to the World Health Organization, 38 million people were living with HIV at the end of 2019.