September 8, 2008

Researchers Link Gene to Key Antibody Responses

A powerful gene controls the production of antibodies that effectively neutralize human retroviruses such as HIV, according to new laboratory research conducted by scientists at the University of California at San Francisco (UCSF) and the Rocky Mountain Laboratories of National Institute of Allergy and Infectious Diseases (NIAID) in Hamilton, Montana. This finding, the authors write in the September 5 issue of Science, may explain why most humans who are infected with HIV do not make neutralizing antibodies that successfully fight the virus.

Antibodies are key to warding off viral infections, and most vaccines against viral diseases stimulate the body to make antibodies against the target virus. Yet no one knows how to make a vaccine that artificially stimulates the production of antibodies that can readily neutralize HIV, largely because so few HIV-infected people naturally exhibit the type of antibody response needed to control the virus.

Genes play a significant role in producing antibodies that successfully neutralize various infections, including retroviruses. Mice are susceptible to a retrovirus called Friend virus, and the UCSF and NIAID researchers point out that a single gene controls the production of neutralizing antibodies that ultimately allow mice to recover from the infection.

A series of experiments led the researchers to conclude that the gene in question is Apobec3, found in both mice and humans. And not only did their data show that Apobec3 contributes to the early control of Friend virus in mice, but the researchers also discovered that a natural defect in the gene correlated with failure to produce an effective neutralizing antibody response to the virus.

The idea that the gene may play a similar role in producing neutralizing antibodies to HIV is supported in studies showing that human Apobec3 proteins exert anti-HIV activity and that the region of the human chromosome containing this gene influences the ability of the virus to establish infection. Research has also demonstrated that HIV uses one of its own proteins, Vif, to destroy two human Apobec3 proteins. Given that Apobec3 seems to help the immune system make neutralizing antibodies against retroviruses, the destruction of Apobec3 proteins by Vif might help explain why most people do not make neutralizing antibodies against HIV.

Search: Apobec3, UCSF, NIAID, antibodies, Vif, Fried virus, vaccine

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