Broadly neutralizing antibodies (bNAbs) that target viral envelope proteins (Env) have significant potential for the treatment of HIV-1. They were initially identified in a small number of patients whose sera were able to inhibit multiple strains of HIV.
These antibodies exhibit a wide range of antiviral activities. In addition to inactivating the virus, i.e. preventing it from infecting new cells, they also destroy infected cells. Therefore, they are called multifunctional molecules.
A full understanding of the range of these antiviral activities is required in order to use existing antibodies more effectively or refine the selection criteria for new antibodies.
Furthermore, it is useful to further investigate the multifunctionality of anti-HIV-1 antibodies to improve our understanding of the role of antibodies and thus address other viral infections. .
Initially, research groups at Institut Pasteur, CNRS, VRI and Universit de Paris sought to determine whether antibodies were able to stop infected cells from making viral particles.
To that end, they cultured CD4 T cells (HIV’s natural target) in vitro with different antibodies for 24 hours. They then measured the number of viral particles produced by the cell in the culture and the number of virus particles remaining in the cell.
As a result of these experiments, the scientists were able to demonstrate that certain antibodies increase the amount of virus in cells but decrease the amount of virus in the culture. This intriguing finding led them to believe that some antibodies interfered with the release of viral particles without inhibiting their production.
To test this theory, the scientists used different microscopy techniques to observe the cell’s production of viral particles. They initially examined the cells with fluorescence microscopy, a technique used to distinguish viral proteins.
This allowed them to demonstrate that infected cells accumulate large amounts of mature viral proteins. This finding suggests that full virus particles accumulate in the cell.
To pinpoint the exact location of these virus particles, the scientists then used scanning electron microscopy to observe the surface of the infected cells.
“Using this approach, we observed that these antibodies (bNAbs) promote the accumulation of viral particles on the surface of the body,” said Timothe Bruel, co-author of the study and a scientist. cell surface, forming clusters and highly atypical structures (see illustration). in the Virus and Immunity Unit at the Pasteur Institute.
Next, the scientists combined transmission electron microscopy with immunolabeling. This allowed them to demonstrate that the antibodies themselves alternate between the viral particles and the infected cell, forming a cluster of chains.
Subsequent experiments with the mutant antibody demonstrated that the Y-shape of the antibody induces this grouping structure. Their arms are capable of binding two viruses, or one virus, to infected cell membranes, and their attachment points are strong enough to cause this.
Olivier Schwartz, final co-author of the study, concludes: “We have demonstrated that only the most potent antibodies bind viral particles on the surface of infected cells. The trapped virus particles are no longer available. can infect new cells”. at the Pasteur Institute.
This work revealed a novel antiviral activity for the widespread inactivation of anti-HIV-1 antibodies. It helps us gain a deeper understanding of how these antibodies work and explain their effectiveness in clinical trials. Scientists are now testing antibodies that target other viruses, including SARS-CoV-2, to determine if they inhibit virus spread through this mechanism.