Important Developments in Dana-Farber's AIDS Research Program
Dana-Farber scientists have been at the forefront of the battle against AIDS since the early 1980s, when the disease was first identified.
In 1989, the Institute was designated by the National Institutes of Health as a Center for AIDS Research, and in 1999 it teamed with Beth Israel Deaconess Medical Center and Boston Children's Hospital to create the DFCI/BIDMC/CH Center for AIDS Research.
Over the past 30+ years, Dana-Farber has been the site of key discoveries into the transmission of human immunodeficiency virus-1 (HIV-1) and the mechanism by which it infects and reproduces in immune system cells. Insights from this work have generated an array of new strategies for blocking the spread of AIDS and treating those with the disease.
Areas where Dana-Farber scientists have made key advances:
- CD4 and CCR5, molecules on immune system cells used by HIV-1 to gain entry to human cells. Dana-Farber investigators demonstrated that a free-floating synthetic version of CD4 can stop the replication of HIV-1 and prevent virally infected cells from latching onto healthy cells. Institute scientists also created a three-dimensional image of CD4 to help identify substances could block the attachment of HIV-1 to certain white blood cells.
- HIV-1's genetic instructions. Scientists discovered that the virus uses a protein called Tat to activate its genes.
- Anti-AIDS drugs. Investigators discovered that the drug AZT prevents replication of HIV-1 and causes no birth defects in pregnant mice infected with the virus.
- The HIV-1 "envelope" protein that encircles the virus. Researchers found that a specific portion of the envelope protein gp120 could be targeted to generate antibodies to block infection by all strains of the AIDS virus. Investigators at Dana-Farber and Columbia University generated the first three-dimensional picture of gp120.
- Immune system impact. Investigators demonstrated that HIV-1 envelope proteins' ability to disrupt cellular membranes is responsible for the destruction of the host cell by the virus. Researchers also showed that HIV infection induces apoptosis (programmed cell death) in brain cell specimens grown in the laboratory.
- HIV transmission. In collaboration with other scientists, Dana-Farber researchers created the first animal model to study how the AIDS virus damages the immune system of a fetus and how virus transmission from mothers to their unborn children, either during pregnancy or during birth, can be prevented.
- HIV replication. Researchers developed a system by which antibodies deliver therapeutic genes to cells by binding to surface receptors. The system is an important step toward the development of a gene therapy for HIV-1 infected patients.
- New drug therapies. Scientists find that an experimental AIDS vaccine that looked promising in adult monkeys proved deadly to newborn monkeys. These findings dampen researchers' hopes that a vaccine made from a weakened form of the AIDS virus might become available in the near future, but redirect scientists toward alternative vaccine strategies that may in the long run prove successful.