The virus that causes AIDS is known to hide in certain rare cells. When people with HIV stop taking their medications, the virus can re-emerge and multiply, or “rebound,” from those hiding places. To better combat HIV, scientists have been working to understand how and why the virus re-emerges.
“It’s the resurrection of virus that you couldn’t see in the body before,” said Jerome Zack, professor of medicine and chair of the UCLA department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA.
Zack, who is director of the UCLA Center for AIDS Research, and colleagues recently received a grant from the National Institute of Allergy and Infectious Diseases called “Defining Factors Controlling HIV Rebound.” The five-year, $7.7 million program will involve three projects.
The projects will investigate factors that accelerate and prevent the re-emergence of HIV, and whether that rebound can be controlled by strengthening the immune system either genetically or by vaccine. The three studies will use mice to track the virus’s development and effects.
“You cannot infect mice with HIV,” Zack said. “The only animals that can be infected with HIV are humans and related species including chimpanzees and gorillas, and we’re not using these as models. But if you take a mouse that doesn’t have its own immune system you can transplant elements of the human immune system into the mice, they will engraft, and then you can infect those human components with HIV.”
Researchers have used this model for more than 25 years to study what HIV does to the body, Zack said.
“We’ve optimized these models so we can now test rebound, which is probably the key thing that is forcing people to remain on HIV drugs, known as antiretroviral therapy, for life,” he said.
Matthew Marsden, an assistant professor of medicine in the division of hematology oncology at the Geffen School, is leading the project on the factors affecting rebound; Zack is heading the genetic engineering component; and Dr. Otto Yang, professor of medicine and of microbiology, immunology and molecular genetics, is investigating vaccination as a way of controlling rebound.
Scott Kitchen, associate professor of medicine in the division of hematology oncology and director of the UCLA Humanized Mouse Core Laboratory, will oversee the work that involves the genetically modified mice. Ren Sun, professor of medical and molecular pharmacology, is overseeing the viral genetics work.
The overall goal of the study is to eventually allow HIV-infected patients to discontinue therapy without the risk of subsequent virus replication.
The researchers have already begun seeing encouraging results. In October 2017, they published research describing an approach toward activating the HIV that lies dormant in cells, causing it to multiply so that either the immune system or the virus itself can kill the cell harboring the virus.
They call it “kick and kill” and, if it works in humans, it could make dependence on antiretroviral therapy a thing of the past.