Researchers Retract Key Finding in Study of HIV-Positive Long-Term Survivors Published 16 Months Ago
Dr. David Ho of the Aaron Diamond AIDS Research Center in New York and colleagues in the Jan. 23 issue of the journal Science retracted the key finding of a study of HIV-positive long-term survivors that identified a family of proteins that block HIV replications, the San Francisco Chronicle reports (Russell, San Francisco Chronicle, 1/23). The researchers in September 2002 published a study in the journal Science in which they announced that they had identified a family of three proteins present in HIV-positive long-term non-progressors that block HIV replication and could reveal a new way to combat the disease. The proteins, called alpha-defensins -- which are found in white blood cells called neutrophils that attack bacteria and parasites and not viruses like HIV -- were first discovered in 1985 and function as natural "antibiotics." Ho's team reported that they found alpha-defensins in CD8+ T cells, a type of immune cell in which alpha-defensins had previously not been identified. Dr. Jay Levy of the University of California-San Francisco was the first researcher to reveal that CD8 cells exhibited a protective antiviral factor, which he called CAF, in some people with HIV. Between 1% and 5% of people with HIV can live untreated with the disease for 10 to 15 years or more without developing AIDS-like symptoms due to an unknown immune response in their body, which researchers have been attempting to identify for years. In a quest to find CAF, which Levy has not been able to identify, Ho and colleagues drew CD8 cells from three long-term non-progressors. The cells were cultured, and then HIV and CD4+ T cells -- HIV's main target -- were added to the cultures. HIV was unable to infect the CD4 cells in the presence of the cultured CD8 cells. The researchers then added antibodies against the three defensins to cultures, essentially inactivating them. When HIV and CD4 cells were added, the cells were "easily" infected, the researchers reported. The researchers performed other tests, including washing the CD8 cells over a new kind of protein chip developed by Ciphergen Biosystems of Fremont, Calif., to prove that the defensins were present. The chips were then read by a mass spectrometer to determine their weight, and the alpha-defensins were identified (Kaiser Daily HIV/AIDS Report, 9/27/02).
Ho and colleagues in a letter to Science titled "Retraction of an Interpretation," wrote that the antiviral factor they had identified did not come from the white blood cells donated by healthy HIV-positive participants, according to the Chronicle. Instead, the researchers said that the factor likely came from a protein produced by a "mixture of blood cells routinely used in the laboratory to make CD8 cells mature," the Chronicle reports (San Francisco Chronicle, 1/23). The retraction comes after two studies -- one led by Levy, who is also editor-in-chief of the journal AIDS, and one by Dr. Mary Klotman, chief of Mount Sinai School of Medicine's infectious diseases division -- that found defensins could not be found in CD8 cultures, the New York Times reports. But Ho and study co-author Dr. Linqi Zhang said that they identified the error "on their own," according to the Times (Pollack, New York Times, 1/23). Levy said, "The paper confused the field and led many to believe that alpha defensins were CD8 antiviral factors. ... But it's good that they took the initiative to write the retraction." He added that his laboratory will continue working to identify "the exact character and composition of the elusive [antiviral] factor," according to the Wall Street Journal (Chase, Wall Street Journal, 1/23). In the letter, the researchers added that they were not retracting the entire article, only the finding that defensins originated from CD8s, saying, "All of our conclusions, except for one, were valid" (San Francisco Chronicle, 1/23).