In the film "Philadelphia," a senior lawyer notices a purplish spot onthe forehead of a subordinate played by Tom Hanks. Hanks dismissesthe spot as a bruise. This plot-point is the beginning of the younglawyer's fight against discrimination and AIDS. The "bruise" wasthe first sign and the characteristic mark of Kaposi's sarcoma (KS),the cancer that most frequently affects AIDS patients.
Before AIDS, KS was extremely rare and when it did appear, itstruck elderly Mediterranean men. Then, during the dark ages of theAIDS era, the 1980s, KS became the face of AIDS. For many, it stillis. Today, KS is far too familiar but perhaps a little better understood.In 1994, a new herpes virus, human herpes virus 8 (HHV8), wasdetected in KS tissue derived from AIDS patients. It immediatelybecame a suspect in the etiology of KS. Scientists also observed thatKS is much more common in AIDS patients who became infectedthrough sexual contact than in patients who received HIV-taintedblood. This implied a sexually transmitted agent.
Now two papers in the August Nature Medicine suggest that HHV8plays an important, perhaps essential, role in the development of KS.They indicate that HHV8 is transmitted sexually and that, unlike mostherpes viruses, it may not be ubiquitous or widespread in the generalpopulation. The authors of both papers looked for antibodiesassociated with HHV8 in blood serum from different populations ofHIV-positive and HIV-negative humans. The results of theserological assays show that as many as 88 percent of KS patientstested positive for the antibody. Approximately 30 percent to 35percent of HIV-positive, but KS-negative, men also had the herpesantibody in their blood.
The antibody was largely absent, however, from subjects free of HIVincluding blood donors and women who have never had vaginalintercourse. Furthermore, few of the subjects who were infected byHIV-tainted blood products tested positive.
Altogether, the two studies tested more than 1,500 subjects for HHV8antibodies (the two groups used similar assays) and showed that thepresence of HHV8 is closely associated with the risk of developingKS.
"These papers are consistent with several earlier studies indicatingthat the virus HHV8 is probably not ubiquitous and itepidemiologically tracks with KS," said Harold Jaffe, associatedirector for HIV/AIDS, National Center for Infectious Disease at theCenters for Disease Control and Prevention (CDC) in Atlanta.
In addition to AIDS patients, KS is seen in HIV-negative individualsreceiving immunosuppressive drugs and in certain subgroups inAfrica and in the Mediterranean region. First author Shou-Jiang Gaoand his co-authors found that the higher incidence of KS in CentralAfrica was reflected in more seropositive findings among Ugandans.Also, more than half of the AIDS-KS patients in the Gao studydeveloped antibodies to HHV8 before they developed KS.
HHV8 Might Be Different
An important and controversial issue in KS research is whether or notthe HHV8 virus is present in nearly everyone. After all, most humanherpes viruses, but not all, are ubiquitous.
"The issue of ubiquitousness is complicated and not resolved," saidDon Ganem, of the Howard Hughes Medical Institute and theUniversity of California. Ganem is senior author of "Theseroepidemiology of human herpes 8 [Kaposi's sarcoma-associatedherpesvirus]: Distribution of infection in KS risk groups and evidencefor sexual transmission," in the August Nature Medicine.
"Both studies show that only a small minority of blood donors havebeen exposed to HHV8," Ganem said, "We know that the other 98percent are not positive in our test. We can't say for sure that thosepeople have never been infected. So I prefer the term `seronegative'for those people rather than `uninfected.'"
Patrick Moore, of Columbia University in New York, and seniorauthor of the Gao paper (titled: "KSHV antibodies amongAmericans, Italians and Ugandans with and without Kaposi'ssarcoma") said the two studies provide strong evidence that HHV8 isnot ubiquitous.
"In my mind this is very good evidence that the virus is causal for thetumor," Moore told BioWorld Today. "Mother Nature could beplaying a big joke on us. It could be ubiquitous and it could be in allpopulations equally," he added, "but there is no data that I can get myhands on that clearly even hint that that is the case."
Other researchers such as the CDC's Jaffe, point to some publishedand some unpublished data that suggest HHV8 is a common infectionand so might not be an important factor in KS. "These two studies dosuggest the virus is not ubiquitous but other studies, particularly oneslooking at HHV8 by detection of DNA, suggest that it is morecommon. At this point I don't think we know which sets of results arecorrect," Jaffe said.
Ganem said many people are much too hung up on the issue of`ubiquitousness.'
"It is not unimportant but it is a separate issue. If it is ubiquitous, itdoesn't say it is unrelated to KS," he explained. "That is what isimportant here. We already have developed a blood test for a form ofthis infection that is already very highly linked to KS."
The virus, Ganem maintains, is important whether it is ubiquitous ornot. "Preventative methods against that form of infection, be theyvaccine or drug-related, might be expected _ if this is all correct _ toreduce the risk of KS. It means this is a potential therapeutic target,"Ganem said. n
-- Dean A. Haycock Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.