Los Angeles Times (01.09.2014)
The Los Angeles Times reported on a study in which an antibody and toxin mix was successful in detecting and killing HIV-infected cells hidden in organs and bone marrow of mice genetically altered to have a human immune system. Researchers developed the altered mice approximately eight years ago, so that they could be infected with HIV similar to humans. The infected mice respond like humans to antiretroviral therapy (ART), but do not get AIDS and scientists can perform assays of mice organs that cannot be done easily on humans. The experiment used the “kick and kill” strategy to arouse silent HIV so antibodies can find and kill it. University of North Carolina Virologist J. Victor Garcia, lead author of the study, explained that the virus continues to produce ribonucleic acid (RNA) in an infected individual’s organs and ART does not stop it. The antibody-toxin mix is aimed at killing these residual cells in the tissues.
The researchers used an antibody that recognizes a protein from the virus on the surface of an infected cell. When the cell expresses the protein, the antibody binds to it, but the antibody cannot kill the cell, so the bacterial toxin in the compound kills it. The experiment targeted cells that express this specific protein, which is part of the active HIV reservoir. The researchers are seeking ways to induce the silent HIV to betray its location and allow antibodies to dock and deliver toxins. Garcia used a truncated version of a bacteria endotoxin carried by a well-tested antibody that targets the GP120 envelope protein that helps HIV enter human immune cells.
Mice that received ART and the antibody toxin had a thousand times greater decrease in virus RNA in bone marrow compared to those that received ART only. The mix also decreased viral RNA in mouse thymic tissue, spleen, lymph nodes, liver, lung, intestines, and blood cells. There was an approximately 100 times decrease in the number of cells producing viral RNA, showing that cell death had a direct effect on viral load.
The full report, “Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART,” was published online in the journal PLOS Pathogens (2014; doi: 10.1371/journal.ppat.1003872).