Antibodies critical for fighting West Nile Virus infection

Researchers at Washington University School of Medicine in St. Louis have found that immune cells called B cells and the antibodies they produce play a critical early role in defending the body against West Nile Virus. The results are published in the February issue of the Journal of Virology.

Mice that lacked B cells and antibodies were completely unable to combat the virus. They developed serious brain and spinal-cord infection and ultimately died.

“These findings may help explain why the elderly and others with weakened immunity are most likely to develop serious disease when infected by the virus,” says study leader Michael S. Diamond, M.D., Ph.D., assistant professor of medicine, of molecular microbiology and of pathology and immunology.

West Nile Virus first emerged in the eastern United States in 1999 and has spread steadily westward, reaching the West Coast last year. It is carried by mosquitoes and causes encephalitis, a brain inflammation. The virus affects mainly birds, especially crows and jays, but it also can cause disease in horses, humans and other mammals.

In humans, West Nile Virus causes serious illness in only a small proportion of infected people. Last year, doctors reported more than 3,500 cases of infection, with 5 to 10 percent of those resulting in serious illness or death.

Diamond and his colleagues infected a strain of immune-deficient mice that lacked two important components of the immune system — T cells and B cells — and compared the animals’ response to mice with normal immunity. T cells coordinate immune responses and kill infected cells; B cells produce antibodies that attack viruses before they infect cells.

The immune-deficient mice became sick and died even with low doses of the virus. However, they could resist infection if given a dose of B cells after being injected with the virus.

“We were surprised by how susceptible the mice were when antibodies were missing,” says Diamond. “Just one viral particle — an exceedingly low dose — was enough to kill the mice.”

To confirm the importance of B cells and antibodies in defending against West Nile Virus, the researchers then gave the virus to a group of immune-deficient mice that lacked only B cells and antibodies, again comparing their response to mice with normal immunity. At day two, both the B-cell deficient mice and normal mice had equal levels of the virus in the blood. The levels declined thereafter in the normal mice and were undetectable by day six. In the B-cell deficient mice, however, viral levels continued to increase, with 500-fold higher levels by day four.

From this, the investigators conclude that B cells and antibodies appear to be essential for controlling the infection.

“Our findings suggest – but this is just speculation – that humans who have weak antibody responses early during infection are more likely to develop serious disease,” says Diamond. “Those are the people we’d want to target when a vaccine or treatment becomes available.”

Diamond and his colleagues now are studying how antibodies control infection and what other parts of the immune system are involved.

Diamond MS, Shrestha B, Marri A, Mahan D, Engle M. B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile Encephalitis Virus. Journal of Virology, February. 2003.

Funding from the National Institute of Allergy and Infectious Diseases supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.