Researchers at the Gladstone Institute of Virology and Immunology have discovered the mechanism that enables some CD4 cells--the main target of HIV--to escape infection. AIDS experts had previously theorized that HIV lacked some key component necessary to recognize and infect resting CD4 cells, but Gladstone director Warner C. Greene and colleagues report in the April 13 online version of the journal Nature having discovered that resting CD4 cells themselves actively work to prevent HIV infection. They found that a key antiviral factor called APOBEC3G exists in the body in two forms--a large chain that is ineffective in preventing cellular infection and a shorter form that repels the virus. Activated CD4 cells carry the longer form the virus, which allows them to be easily infected with HIV. But resting CD4 cells carry the smaller chain of the compound, which makes them impervious to HIV infection. Lab tests showed that blocking the effects of the small form of APOBEC3G in resting CD4 cells suddenly made them susceptible to HIV infection.
Greene's group is now looking at ways to use this new knowledge therapeutically. One approach would involve converting the ineffective, large chain of APOBEC3G into the protective, small form in activated CD4 cells to help them also resist infection. A parallel strategy would involve finding ways to prevent the small form of APOBEC3G from converting to the large form during the process of CD4 cell activation.
