An Unprecedented Cocktail to Curb HIV

Researchers at the Center hospitalier de l’Universite de Montreal (CRCHUM) and Yale University researchers have succeeded, on humanized mice, in reducing the size of the reservoir where HIV is hiding 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 at 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 composed of two antibodies naturally present in the plasma of people infected with HIV and a small molecule ‘can opener’, we have succeeded in exposing and stabilizing a vulnerable form of the envelope of the virus. 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 the CRCHUM and professor at the University of Montreal.

To infect cells of the human immune system, HIV attaches itself with its envelope to specific receptors on the surface of these cells, including one called CD4. This binding triggers changes in the shape of the virus’s envelope, its entry “key”, and allows it to infect host cells.

In 2019, in an earlier study, a team led by Andres Finzi and James Munro (Tufts University) found that small molecules resembling CD4s, designed and synthesized by the team of researcher Amos Smith, from the University of Pennsylvania, behaved like “can openers” and allowed the virus to be forced open and exposed vulnerable parts of its envelope.

“On our humanized mouse model designed at Yale and used for the study of HIV, we show that the cocktail allows not only to limit the replication of the virus, but also to decrease the reservoirs of HIV by destroying the infected cells”, explains Priti Kumar, lead author of the study and professor at Yale University.