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.
The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation's oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 48,000 people were treated at Mount Sinai as inpatients, more than 72,000 received care in the emergency department, and the outpatient department recorded nearly 470,000 visits. Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as innovative approaches to medical education. Mount Sinai ranks 9th among the nation's 125 medical schools in the percentage of graduates who go on to faculty positions in medical schools across the country. Mount Sinai also is in the top 25 in receipt of National Institutes of Health (NIH) grants with a total of more than $154 million during Fiscal Year 2003. Information about Mount Sinai can be found online at: www.mountsinai.org and www.mssm.edu
Journal
Journal of Clinical Investigation