Scientists at the National Institute of Mental Health (NIMH) Laboratory of Molecular Biology, reporting in the August 24, 2001, issue of Science Magazine, have discovered an unexpected step in the process that the human immunodeficiency virus (HIV) uses to get around natural barriers, infect human cells, and eventually cause AIDS.
HIV replicates predominantly in the subset of blood cells called CD4 T cells, and the loss of these cells results in immunodeficiency. Most T cells are in a resting state, a condition that resists HIV infection. The researchers found that HIV has evolved a way around this natural barrier.
NIMH Director Steven E. Hyman, M.D., said, " This work further demonstrates the subtle ways in which HIV avoids the body's natural resistance to infection. Our understanding of these evolved mechanisms better prepares us to attack this deadly virus."
HIV belongs to a class of viruses called retroviruses whose genetic structure, or genome, is composed of RNA, differing, for example, from the human genome, which is composed of DNA. After entering a human cell, the HIV RNA manufactures a DNA copy of its RNA, which then gets integrated into the human cell's DNA. After this integration, the viral DNA acts very much like a normal human gene, but rather than making proteins that are essential for human life, it makes new virus particles. Retroviruses such as HIV must integrate into the human cell's DNA in order to replicate.
The new study shows that after the viral RNA's manufacture of the DNA copy, but prior to the viral DNA's integration into the cellular DNA, the HIV DNA serves as a template to make viral proteins called Nef and Tat, which bring the CD4 T cells out of their resting state, allowing the virus to integrate into the cellular DNA and replicate.
Scientists have previously shown that persons infected with HIV have many cells in the brain and elsewhere that contain non-integrated HIV DNA. Although non-integrated DNA cannot produce new virus, these new findings show that it does contribute to disease progression.