Probable New Herpesvirus Linked to Kaposi's Sarcoma

The 20-year search for an infectious agent associated with Kaposi'ssarcoma (KS) may be over. Researchers at Columbia-PresbyterianMedical Center in New York have reported significant evidencedirectly linking a probable new herpesvirus to KS in AIDS patients.

Dr. Yuan Chang, Assistant Professor of Pathology at Columbia UniversityCollege of Physicians & Surgeons, and Dr. Patrick Moore, AssistantProfessor of Public Health at Columbia University School of PublicHealth, co-principal investigators of the research, found uniqueDNA sequences from what may be a new type of human herpesvirusin 93% of KS lesions from 27 deceased AIDS patients. The sequencesgenerally were not found in the patients' non-KS tissues.

The DNA sequences found in the KS lesions are most similar tothe DNA sequences of a group of herpesviruses known as gamma-herpesviruses.The new virus, which is thought to be sexually transmitted, ismost closely related to the Epstein-Barr virus.

The Columbia researchers' findings open the way to potential improvementsin the diagnosis and treatment of KS patients, and provide onemore example, among only a handful, of a virus being implicatedin cancer causation.

"Ours is the first evidence, as far as I know, of a reliablemolecular marker, DNA sequences, found specifically in KS tissue,"says Dr. Chang. The investigators also tested the reliabilityof their molecular marker by correctly predicting KS in 11 tissuesamples provided to them blindly from the University of Pittsburgh.

At present, these findings do not change the standard treatmentfor KS. It is not yet known whether drugs that are currently effectiveagainst herpesviruses would have any effect on this presumed virus.In the future, however, a diagnostic test or therapeutic agentcould be developed based on the DNA sequence, or from antibodiesraised against the virus.

"If we can prove that this putative virus actually causesthe cancer, diagnostic tests could be developed that might helpclinicians determine sooner who may be at risk for developingKaposi's sarcoma," says Dr. Chang.

For some time, epidemiologists have thought that a sexually transmittedagent might be responsible for the KS disease pattern seen ingay and bisexual AIDS patients. Gay and bisexual men with AIDSare 20 times more likely than hemophiliacs to develop KS (Lancet,335:125, 1990). Women with AIDS also are more likely to developKS if their partners are bisexual men rather than intravenousdrug users.

"While we have no direct evidence that KS is sexually transmitted,the higher rates among gay and bisexual men with AIDS, comparedto hemophiliacs with AIDS, suggest that it might be sexually transmitted,"says Dr. Moore. "For now, it is prudent to say that safesex practices, besides preventing the spread of HIV, probablymay prevent the transmission of this presumed herpesvirus."

Dr. Moore adds that there may be multiple modes of transmissionof the new virus, and there is no evidence that it can be transmittedcasually. The virus was not found in tissue from 85 individualswithout AIDS or KS, indicating that it is probably not commonto the general population. The researchers currently are determiningwhether the viral DNA sequences they found are present in KS lesionsof non-AIDS patients.

Infectious agents suspected of causing KS over the past 20 yearsinclude viruses, such as cytomegalovirus, hepatitis B virus, humanherpesvirus 6, and HIV; and bacteria, such as Mycoplasma penetrans.Even noninfectious agents, such as nitrite inhalers, or poppers,a drug used by the gay community, were thought to be a cofactorfor KS. "Extensive research has not demonstrated a causalrelationship between these agents and KS in AIDS," writethe scientists.

Drs. Chang and Moore used the latest tools in molecular biologyanalysis-representational difference analysis and the polymerasechain reaction-to isolate the extraneous viral DNA sequences.They have identified portions of three separate genes that appearto belong to this new virus. The sequences also have been foundin lymphoma tissue and lymph nodes from 3 of 39 other AIDS patients.The role of the sequences in AIDS-associated lymphomas is beinginvestigated.

Although the scientists believe that they have strong evidenceimplicating the virus as the causative agent of KS in AIDS patients,they need to do additional work to prove it. "Although thisvirus is not found in most non-KS tissue, it is still possiblethat this agent is a common latent virus in humans that preferentiallycolonizes KS lesions in immunocompromised patients," theauthors say.

If this presumed herpesvirus is shown to cause KS, it would beanother addition to the list of viruses known to cause cancer.These include papillomavirus (cervical cancer), hepatitis B (livercancer), and Epstein-Barr virus (Burkitt's lymphoma and nasopharyngealcarcinoma).

Drs. Chang and Moore, a wife and husband team, took a year toidentify the sequences with their collaborators. The other investigatorson the project were Drs. Ethel Cesarman and Daniel Knowles, formerlyof Columbia-Presbyterian Medical Center but now with Cornell MedicalCenter in New York City; Dr. Melissa Pessin, a postdoctoral fellowin Columbia's Department of Pathology; and Drs. Frank Lee andJanice Culpepper of DNAX Research Institute in Palo Alto, California.

This research was funded by start-up funds from Columbia's Departmentof Pathology and the School of Public Health. The full reportis published in Science, Vol 266:1803-1804.