Edited by: Thomas W. Durso Comments by Patrick S. Moore, division of epidemiology, Columbia University School of Public Health.
P.S. Moore, Y. Chang, "Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and those without HIV infection," New England Journal of Medicine, 332:1181-5, 1995. (Cited in more than 165 publications as of April 1997) E. Cesarman, Y. Chang, P.S. Moore, J.W. Said, D.M. Knowles, "Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas," N. Engl. J. Med., 332:1186-91, 1995. (Cited in more than 160 publications as of April 1997)
Comments by Patrick S. Moore, division of epidemiology, Columbia University School of Public Health.
Kaposi's sarcoma (KS), a cancer-like disease of the skin, once seemed to be limited to elderly heterosexual men of Mediterranean, Middle Eastern, and Eastern European descent. Now researchers are finding that KS is also common among gay men-regardless of their HIV status.
In December 1994, a team of researchers from Columbia University and the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto, Calif., reported isolating a pair of DNA sequences from KS lesions of people with AIDS (Y. Chang et al., Science, 266:1865-9, 1994). While the DNA sequences were not found in tissues of healthy individuals, they did show up in some tissues from AIDS patients, particularly in lymph nodes and several lymphomas. The team concluded that the DNA probably belonged to a new herpesvirus associated with KS; however, with the available evidence, this virus could not be proved to cause KS.
CONSIDERING KS: Columbia's Patrick Moore and Yuan Chang found strong evidence that a new herpesvirus causes Kaposi's sarcoma.
"At the time of the Science article, we had good evidence that the virus might be a cause of Kaposi's sarcoma, but it was certainly not proven at that point in time," Moore recalls. "We had not shown that it was present in all forms of Kaposi's sarcoma. We had only shown it was present in AIDS KS patients."
While the initial findings in the Science paper led the researchers to question if the virus was easily detected in AIDS patients because their immune systems were vulnerable, this paper showed that wasn't the case. "All forms of KS appeared to be positive for the virus," says Moore.
In the second paper, Moore, Chang, and collaborator Ethel Cesarman of the New York Hospital-Cornell Medical Center described finding the virus in a particular subset of lymphomas called body cavity-based lymphomas. "These are AIDS lymphomas that don't form a tumor mass," Moore says. "Most [lymphomas] do form a tumor mass in the lymph nodes. With this, the cells grow as a malignant fluid-effusion in body cavities."
Finding the virus in body cavity-based lymphomas has enabled scientists to determine how to grow the virus in tissue cultures. "Whereas the virus could not be grown directly from KS lesions, it could be grown from tissue culture," Moore states. "Therefore, we have a ready source of virus that's growing, and we're able to perform virology on it."
Asked why he thinks the papers have been highly cited, Moore responds: "The real controversial issue about this virus is whether it actually causes Kaposi's sarcoma or not. The first paper lends strong evidence that all of the various forms of Kaposi's sarcoma belong to one underlying disease mechanism, [and] that it's related to this virus." As for the second paper, it "provides the basic foundation for the virological studies which are being performed that allow us to grow the virus in tissue culture." This is being used "to develop antibody assays to determine how common the virus is in the general population and how we can develop reagents that allow us to look at the virology of this unusual herpesvirus."
Since these papers were published, Moore and Chang have continued researching the KS herpesvirus. Among their accomplishments was the sequencing of its genome (J.J. Russo et al., Proceedings of the National Academy of Sciences, 93:1486-7, 1996).
Moore concludes: "I don't think it's going too far to say that this virus is something of a Rosetta stone-perhaps an imperfect one-but a Rosetta stone for telling us what are common features among the various DNA tumor viruses."