Biomedical Frontiers: Winter 1995, Vol.2, No.2
Herpesvirus Linked to Kaposi's Sarcoma

The 20-year hunt for an infectious agent associated with Kaposi's sarcoma may now be over. A team of Columbia-Presbyterian Medical Center researchers have characterized 20 kilobases of DNA sequence from a new type of herpesvirus capable of growing in continuous culture and isolated from Kaposi's sarcoma tissue of an AIDS patient.

The findings, reported at the Jan. 29th meeting of the Second National Conference on Retroviruses and Related Infections, comes on the heels of results published in the Dec. 16, issue of Science. Earlier, the scientists would only say they had identified novel herpesvirus-like DNA sequences from Kaposi's sarcoma patients.

At the meeting, Dr. Patrick Moore, assistant professor of public health and co-principal investigator of the Science paper, said his laboratory had sequenced genes from this new herpesvirus that are homologues to the thymidine kinase, the glycoprotein H-1, the major capsid protein, and several minor capsid and glycoprotein genes from gamma herpesviruses.

He also said his laboratory found the virus in Kaposi's sarcoma patients who were not infected with the AIDS virus.

The scientists found these DNA sequences in 93 percent of Kaposi's sarcoma (KS) lesions from 27 deceased AIDS patients. The sequences generally were not found in patients' non-KS tissues.

The work opens the way to potential improvements in the diagnosis and treatment of Kaposi's sarcoma (KS) in AIDS and non-AIDS patients and provides one more example, among only a handful, of a virus implicated in cancer causation.

"If we can prove that this putative virus actually causes the cancer, diagnostic tests could be developed that might help clinicians determine sooner who may be at risk for developing Kaposi's sarcoma," says Dr. Yuan Chang, assistant professor of pathology and co-principal investigator on the paper.

"Improved treatments someday are also a possibility," says Dr. Moore. "But at present these findings do not change standard treatments for KS. For now it is prudent to say that safe sex practices, besides preventing the spread of HIV, may probably prevent the transmission of this herpesvirus. But even if this cancer is due to a new virus, there is no evidence that it can be casually transmitted," adds Dr. Moore.

For some time, epidemiologists, such as Dr. Harold Jaffe and Dr. Valerie Beral of the Centers of Disease Control and Prevention in Atlanta, have thought a sexually transmitted culprit might be responsible for the KS disease pattern seen in homosexual and bisexual AIDS patients. Homosexuals and bisexuals with AIDS are 20 times more likely than hemophiliacs to get KS, Drs. Jaffe and Beral wrote in Lancet in 1990 (Vol. 335: p.125). Women with AIDS also are more likely to develop KS if their partners were bisexual men rather than intravenous drug users.

Infectious agents suspected of causing KS for the past 20 years included viruses and bacteria. Even non-infectious agents, such as nitrite inhalers, or poppers, a drug used by the gay community, were thought to be a co-factor for KS.

"Extensive research has not demonstrated a causal relationship between these agents and KS in AIDS," say the scientists in the paper.

"Ours is the first evidence, as far as I know, of a reliable molecular marker found specifically in KS tissue," says Dr. Chang.

In the Science paper, the researchers used the latest tool of molecular biology-representational difference analysis and the polymerase chain reaction-to isolate the extraneous and unique herpesvirus-like DNA sequences in KS but not normal tissue of a deceased AIDS patient. They assumed they found a virus because the sequences are found primarily in KS tissue and not in non-KS tissues from KS patients, and the sequences are closely related to other herpesviruses.

The scientists suspect the herpesvirus may play a role in KS because the virus-like sequences are present in all AIDS patients sampled. (Two KS samples were negative for these sequences due to technical reasons.) They also found the sequences in lymphoma tissue and lymph nodes from 6 of 39 other AIDS patients. They are investigating the role of the sequences in the AIDS-associated lymphoma. They did not detect the sequences, however, in a variety of biopsy tissues from 85 patients who did not have AIDS or KS.

With their molecular marker, the researchers correctly predicted KS in 11 tissue samples provided to them blindly from the University of Pittsburgh. In the future, a diagnostic test or therapeutic could be developed based on the DNA sequence or from antibodies raised against the virus.

Although the scientists believe they have strong evidence implicating the virus with KS in AIDS patients, they need to do additional work to prove it. "It is possible that this agent is a common latent virus in humans that preferentially colonizes KS lesions in immunocompromised patients," the authors say.

If they can prove that this presumed herpesvirus causes KS it would be another example of virus responsible for cancer. Other viruses known to cause cancer include papilloma virus (cervical cancer), hepatitis B (liver cancer), and Epstein-Barr virus (Burkitt's lymphoma and nasopharyngeal carcinoma).

Drs. Chang and Moore, a wife and husband team, took a year to identify the sequences with their many collaborators.