Mar. 18, 2005 New York - Researchers at Mount Sinai School of Medicine have found alpha-defensin-1, a protein found in immune cells, can control HIV infection by at least two mechanisms. Earlier studies have primarily looked at the role of defensins in bacterial diseases. A study published the March 1 print edition of the Journal of Clinical Investigation (JCI) examines their role as natural antiviral substances.
Theresa Chang and colleagues at Mount Sinai School of Medicine analyzed how alpha-defensin-1 inhibits HIV infection in white blood cells (CD4+ T cells). Defensins have been shown to have anti-HIV activity. The body attempts to protect itself from HIV infection via the innate immune system.
"Understanding the mechanism by which natural host defenses work against viruses such as HIV will give us insight into understanding the host virus relationship," says Theresa Chang, PhD, first author of the study and Assistant Professor of Medicine at Mount Sinai School of Medicine. "This study suggests they may be quite important not only to HIV but to other viral infections."
The researchers show that alpha-defensin-1 fights HIV in two different ways. Without serum (the watery portion of blood that remains when blood cells are removed) where viral burden is low, alpha-defensin-1 directly inactivates HIV virus. When serum is present, alpha-defensin-1 acts on vulnerable cells to block HIV infection. The authors also show that the way alpha-defensin-1 blocks HIV infection in cells is by inhibiting a CD4+ cell-signaling molecule called PKC.
"Understanding the complex interactions by which a-defensins make a cell less susceptible to HIV may open new avenues to explore for prevention and therapy," says Mary E. Klotman, MD, senior author and Chief of Infectious Diseases at Mount Sinai Medical Center.
The findings offer insight into the function of alpha-defensin-1 on both the virus and the cell and the innate immunity against HIV. In addition, this study provides a basis to develop defensin-like drugs for prevention of HIV and for therapeutic use in patients who are already infected.
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