A new gene that may influence the production of antibodies that neutralize HIV has been identified by a team of researchers at the Gladstone Institute of Virology and Immunology (GIVI) and the National Institutes of Allergy and Infectious Diseases (NIAID).
According to the researhcers, the new finding will likely spur a new approach for making an HIV vaccine that elicits neutralizing antibodies.
In 1978, researchers at the National Institutes of Health (NIH) studying a similar retrovirus in mice discovered a gene called Rfv3 that influenced the production of neutralizing antibodies that allowed the animals to recover.
By 1999, they had narrowed the location of Rfv3 to a relatively small region on mouse chromosome 15, but that region contained more than 60 genes.
The laboratory of GIVI Director Warner C. Greene and a team of scientists from NIAID now demonstrate that Rfv3 is Apobec3, an innate immunity gene with antiretroviral activity.
"This newfound link between Apobec3 and the production of neutralizing antibodies came as a complete surprise," said Dr. Greene, senior author of the study.
HIV uses one of its genes, Vif, to specifically disable human Apobec3 proteins and HIV-infected patients rarely make broadly neutralizing antibodies against this virus.
This new study raises the possibility that drugs or vaccines that interfere with Vif might allow humans to naturally make better neutralizing antibody responses against HIV.
Gladstone scientist Mario Santiago, PhD, said: "We now have a host factor needed for the production of neutralizing antibodies that HIV targets and destroys. This offers a fresh perspective on how to strengthen this arm of the immune response against HIV, with direct implications for immunotherapy and vaccine development."
The researhcers conducted a series of genetic experiments by mating mice with different Rfv3 and Apobec3 profiles.
The researchers demonstrated that Apobec3, like Rfv3, contributes to the early control of retroviral infection in mice, and also influences specific retroviral antibody responses.
Also, they discovered that Rfv3 susceptible mouse strains that fail to make antibody responses have a natural defect in Apobec3. These results provide convincing evidence that Rfv3 and Apobec3 are the same gene.
"We set out to solve a 30-year old mystery in retrovirus biology and in the process made a discovery that might impact future development of HIV vaccines," said Dr. Greene.
The study is published in the September 5 issue of Science.