A small protein in human saliva blocks the AIDS virus from infecting human cells in the test tube, Federal scientists reported at a meeting here last week. The protein might help explain why the spread of the virus through saliva is apparently so rare, said the scientists, who were from the National Institute of Dental Research in Bethesda, Md.
The protein does not directly attack H.I.V., the AIDS virus. Instead, it seems to act indirectly, by attaching to the surface of white blood cells known as monocytes, thus preventing infection with H.I.V., said Dr. Tessie B. McNeely and Dr. Sharon M. Wahl, the scientific team leaders. They reported the findings at a meeting sponsored by the American Society for Microbiology.
The protein is known as SLPI (pronounced slippy) for secretory leukocyte protease inhibitor. It had been known by different names for many years until 1986, Dr. Wahl said, when its biochemical characteristics were identified through the efforts of Dr. Kjell Ohlsson, a Swedish researcher who identified a small amount from the 1,000 liters of saliva his son, a dentist, had collected in Sweden.
The dental institute team's findings are the result of an effort begun several years ago and grew out of observations made by many epidemiologists and laboratory scientists elsewhere about the nature of H.I.V. and how it spreads.
Almost from the time AIDS was first recognized in 1981, a major public fear was that the disease could be spread by saliva. Shared dishes, dental offices, bites by children playing in school or elsewhere, kissing and oral sex were all feared to be modes of transmission of saliva-borne virus.
But there have been only rare documented cases of H.I.V. transmission through saliva, and virtually all have involved oral sex , said Dr. Harold W. Jaffe, a top AIDS official at the Centers for Disease Control and Prevention in Atlanta. A few rare cases of H.I.V. infection may have been transmitted through saliva mixed with blood, he said.
The few cases of H.I.V. that have been transmitted through oral sex have led the centers to warn against the risks of that practice. But the agency says the risk of contracting H.I.V. from oral sex is much smaller than from vaginal or anal intercourse.
H.I.V. can be recovered from the saliva of infected people, but infrequently and nearly always in low amounts. The low yield has puzzled scientists because larger amounts of H.I.V. can be found in blood, in the fluid that bathes the brain and spinal cord, and other body fluids.
Thus a number of scientists have tested saliva for its anti-H.I.V. effects, and over the last 10 years they have reported finding that it had a general inhibitory effect on H.I.V. Among those reports was one in 1989 from a team headed by Dr. Philip C. Fox at the National Institute of Dental Research. But because Dr. Fox's team did not include laboratory scientists, they could not advance the research by seeking to determine whether specific components of saliva were responsible for the effect, Dr. Wahl said in an interview.
It fell to her team of immunologists and biochemists at the dental institute to do the follow-up studies, Dr. Wahl said, adding, "We were less than thrilled at the time" because they thought the chance of making an important finding was a long shot. The team included Dr. Stephen P. Eisenberg and Dr. David J. Dripps.
To learn whether other body fluids had similar anti-H.I.V. activity, the scientists tested the synovial fluid that lubricates joints and the plasma portion of blood. But they found that there was something unique about saliva's anti-H.I.V. activity. They went on to test several components of saliva other than SLPI to determine whether any prevented infection in white blood cells but made little progress and eventually put the project aside.
One day a representative of Synergen Inc. of Boulder, Colo., stopped to discuss other work with Dr. Wahl and mentioned that his company had some purified SLPI. It was a component that the researchers at the institutes knew little about.
Synergen sent a supply. With further work, the scientists found that when they added SLPI to test tubes containing H.I.V. and monocytes, white blood cells with immune function, the viruses were unable to bind to the surface of the cell and therefore did not infect their usual targets. Tiny amounts of SLPI were strongly protective.
In a further step, the scientists found that even after they had washed SLPI out of the test tubes and added more H.I.V., the monocytes remained protected for three weeks.
"SLPI has as much anti-H.I.V. activity as whole saliva," Dr. McNeely said.
The team knows that SLPI does not react with CD-4, the receptor on the surface of immune cells in the blood that H.I.V. targets for destruction. So the team is now trying to identify precisely how SLPI blocks H.I.V. Because scientists do not have a full understanding of how H.I.V. infects cells, clarifying the mechanism by which SLPI blocks infection could have broader importance.
SLPI is believed to be a natural protector against the body's own protein-destroying enzymes. The protein is found in mucous membranes throughout the body and in low amounts of the blood. Another research goal is to measure amounts of SLPI in the genital-urinary and rectal areas and to determine if low levels contribute to the transmission of H.I.V. through sexual intercourse.
The researchers are also trying to determine whether there are other proteins in saliva that have anti-H.I.V. activity. And they are working with Synergen, which is now owned by Amgen Inc. of Thousand Oaks, Calif., to determine whether administration of SLPI to animals and ultimately humans could protect against H.I.V. infection or modify the virus's damage and improve health.
Like many other findings concerning AIDS, this one may lead to a dead end. But the finding might never have been made without the idle comment made in the Synergen visit to Dr. Wahl's office.
Also discussed at last week's meeting was a major unanswered question: if a way were found to stop replication of H.I.V., could a moderately or severely damaged immune system regain its function? If so, might one beneficial method be injections of proteins known as cytokines produced by the immune system?
Possibly, according to findings reported by Dr. Anthony S. Fauci, the head of the National Institute of Allergy and Infectious Diseases. His team found that intermittent injections of a cytokine known as interleukin-2, or IL-2, when combined with an anti-H.I.V. drug, can produce a striking and persistent rise in the CD-4 count.
IL-2 recipients doubled the number of CD-4 cells from a mean of 400 to a range of 800 to 1,000 cells, which is well within normal range.
The findings were based on a small study of 10 patients who received an infusion of IL-2 for five days every eight weeks. The study has since been expanded.
Of the initial 10 patients, six showed what Dr. Fauci described as a dramatic boost in CD-4 cells. In the remaining four, the immune system seemed to hold steady. The effect was most dramatic in patients who were in relatively good health, with CD-4 counts of 200 or more. In some patients, the response has been so strong that they were able to skip treatments with no drop in CD-4 counts.
Dr. Fauci said that although such results have not been seen with anti-H.I.V. drugs, his team's research was too preliminary to necessarily mean that the therapy would improve the health of the recipients.
The researchers found that the amount of H.I.V. rose slightly after IL-2 treatment, then returned to original levels, apparently because IL-2 stimulates the virus as well as the immune system. Larger trials are under way to determine IL-2's role in H.I.V. therapy, Dr. Fauci said.
In a study involving 11 patients, scientists at Stanford University reported finding that the amount of H.I.V. in the blood of infected people rises sharply after active infection from oral and genital sores caused by herpes simplex virus. The Stanford team, led by Dr. Mark Holodniy, said it was the first direct clinical evidence linking the two viruses.
The amount of H.I.V. was measured before each patient was treated with an anti-herpes drug, acyclovir, and again during and after therapy. The amount of H.I.V. increased about five times during active herpes infections. About 30 to 45 days after acyclovir treatment, the amount of H.I.V. returned to previous levels.