NIH-created toxin can kill HIV-infected cells that persist despite treatment
Approach could potentially be part of future HIV cure strategy
9-Jan-2014 - A team including University of North Carolina and NIH scientists has demonstrated in a mouse
model that an HIV-specific poison can kill cells in which the virus is actively reproducing despite antiretroviral therapy.
According to the researchers, such a targeted poison could complement antiretroviral therapy, which dramatically reduces
the replication of HIV in infected cells but does not eliminate them.
The 40 mice in the experiment were bioengineered to have a human immune system. They were infected with HIV for several months and
then given a combination of antiretroviral drugs for four weeks. Half of the animals subsequently received a two-week dose of a
genetically designed, HIV-specific poison, or immunotoxin, to complement the antiretrovirals, while the other half continued
receiving antiretrovirals alone. The scientists found that, compared to antiretrovirals alone, the addition of the
immunotoxin significantly reduced both the number of HIV-infected cells producing the virus in multiple organs
and the level of HIV in the blood. According to the researchers, these findings, coupled with results from
previous studies, suggest that treating certain HIV-infected people with a combination of antiretrovirals
and an immunotoxin might help achieve sustained disease remission, in which HIV can be controlled or
eliminated without a lifetime of antiretroviral therapy. However, further study is required, the scientists write.
The immunotoxin, known as 3B3-PE38, was created in 1998 in the laboratories of Edward A. Berger, Ph.D., of the National Institute of
Allergy and Infectious Diseases, and Ira Pastan, Ph.D., of the National Cancer Institute, both part of NIH. This genetically modified
bacterial toxin targets HIV-infected cells and becomes internalized by them, shutting down protein synthesis and triggering cell
death. The study was designed by Drs. Berger and Pastan in collaboration with J. Victor Garcia, Ph.D., and colleagues at the
University of North Carolina School of Medicine, where the experiments were performed.
ARTICLE: PW Denton et al. Targeted cytotoxic therapy kills persisting HIV-infected cells during ART. PLOS Pathogens DOI: ppat.1003872 (2014).
NIAID Director Anthony S. Fauci, M.D., and Edward A. Berger, Ph.D., senior investigator in the NIAID Laboratory of Viral Diseases, are available for comment.
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NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov .
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/ .
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