- Posted Monday April 25, 2005
Genes may inhibit replication and transcription of virus
Phoenix, AZ, and Washington, DC April 25, 2005--Using advanced genetic technology, scientists have identified a set of genes that become activated in individuals with HIV-1. These genes may be potential drug targets that one day may lead to therapies that block the progression of the disease. The findings were published recently in the online issue of Retrovirology.
HIV infection and the subsequent development of AIDS are caused by a number of factors including the "hijacking" of cellular functions, which allows the infection to evade immune response. After the body becomes immunodeficient, one protein in particular, HIV-1 Tat, appears to be among the most critical for viral transcription and replication.
Building upon this knowledge, scientists at the Translational Genomics Research Institute (TGen), The George Washington University School of Medicine, Johns Hopkins Medical School, Tampere University of Technology, and the Institute for Genomic Research used expression profiling technology to identify genes that are activated by HIV-1 infection.
"The genes activated by HIV-1 are never turned on in healthy adults. Therefore, these genes are ideal targets for therapy because they are not crucial for normal human functions," said the paper's senior author Fatah Kashanchi, an Associate Professor at the George Washington University School of Medicine.
Using siRNA technology, researchers shut off the "activated" genes and inhibited the ability of HIV-1 to replicate. While some of these genes have already been established as critical for HIV-1 infection and replication, others have not and thus may serve as novel therapeutic targets to be further studied.
"This study is an ongoing attempt to figure out which genes are critical to Tat regulation. This allows us to define a set of potential drug targets that will supplement current HIV therapies," said Dr. Dietrich Stephan, head of TGen's Neurogenomics Division.
The earliest known case of HIV-1 in a human was from a blood sample collected in 1959 from a man in Kinshasa, Democratic Republic of Congo. Genetic analysis of this blood sample suggested that HIV-1 may have stemmed from a single virus in the late 1940s or early 1950s. The Centers for Disease Control and Prevention estimate that 850,000 to 950,000 U.S. residents are living with HIV infection, one-quarter of who are unaware of their infection. Approximately 40,000 new HIV infections occur each year in the United States, about 70 percent among men and 30 percent among women. Of these newly infected people, half are younger than 25 years of age
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The mission of the Translational Genomics Research Institute (TGen) is to make and translate genomic discoveries into advances in human health. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. TGen is focused on personalized medicine and plans to accomplish its goals through robust and disease-focused research programs and its state-of-the-art bioinformatics and computational biology facilities.
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