AIDS virus can get into body through mucous membranes, new studies show


FLORENCE, Italy -- The AIDS virus, long known to be transmitted through the bloodstream, can also enter the body through cells in the mucous membranes, researchers reported yesterday.

Their findings appear to shed light on one of the puzzles of the epidemic: how heterosexual transmission occurs in the apparent absence of sores, tears or other openings that would allow the virus to enter the bloodstream directly.

In two separate studies reported at the Seventh International Conference on AIDS, U.S. and Italian researchers report finding the human immunodeficiency virus in dendritic and mucosal cells. Dendritic cells are usually near lymph nodes; mucosal cells are found in the lining of the genitals, anus and mouth, as well as in semen and vaginal fluids.

"It helps explain heterosexual transmission," said the lead U.S. researcher, Dr. William Haseltine of Harvard University's Dana-Farber Cancer Institute.

"Just as we know the exact routes of transmission for gonorrhea, syphilis and candida, we now have the route for this virus."

It has long been known that the virus can be transmitted when infected blood or semen enters a person's bloodstream. In the United States, HIV is spread mostly by sharing of needles among drug users and by homosexual intercourse. In most of the world, however, it is chiefly spread by heterosexual sex, which usually does not involve bleeding. To explain this, researchers have theorized that genital sores or rough sexual practices may provide a route in to the bloodstream. The new research explains how sexual transmission can occur without such means -- and also suggests that it could occur through oral sex.

The finding, Dr. Haseltine said, means that acquired immune deficiency syndrome should be regarded like other sexually transmitted diseases.

"Look," Dr. Haseltine said, "let's be candid. AIDS is a venereal disease. . . . It's time people stopped thinking there was something special about somebody else that put them at risk for HIV. Mucosa is mucosa; VD is VD."

Neither dendritic nor mucosal cells have CD4 receptors, special proteins long thought to be the doorknobs that HIV uses to gain entry into a cell. For the last 10 years, AIDS researchers have assumed that the primary target for HIV was CD4-bearing T cells of the immune system.

But, Dr. Haseltine said, it is beginning to look as if the dendritic cells are the first target of the virus and that T cells are secondary.

Last year, Harvard's Dr. Jerome Groopman reported finding HIV in Langerhans cells, which are dendritic cells of the pancreas. Dendritic cells have long finger-like projections that capture viruses and pass them into lymph nodes, where they come in contact with cells of the immune system.

Mucosal cells -- known as M cells -- are small, odd-shaped sticky bodies that are interspersed among epithelial cells that form the lining of such sites as the vagina and anus. The polio virus also enters the body through M cells, Dr. Mark Poznansky of Dana Farber said.

"They are like a special window for the virus," Dr. Haseltine said. "Asfar as we know the M cells are not actually infected. But they're sticky. The virus gets stuck on the M cell surface, absorbed inside and then passed to the other side. The M cells are, in a sense, virus transportation."

A study to be presented today at the AIDS conference by Dr. Giovanna Zambruno of the Institute of Biochemical and Evolutionary Genetics in Pavia, Italy, says that viral genetic material was found in the dendritic cells of seven of nine AIDS patients who were studied. Another study, by researchers from St. Vincent's Hospital in Sydney, Australia, found HIV in cells between the mucosa and the bloodstream.

The discovery poses new challenges for AIDS vaccine researchers, Dr. Haseltine said, because it shows that the virus can enter the body by hiding inside cells, away from the bloodstream where vaccine-induced antibodies might recognize and challenge the invaders.

"It doesn't make vaccines impossible; it just makes them difficult," Dr. Haseltine said, noting that the current vaccines under development elicit antibodies of the IgG or IgM classes, which would fight HIV in the bloodstream but not in the mucosa. IgA antibodies would be needed to fight the virus in the mucosa.

Dr. Poznansky said the Sabin oral polio vaccine elicits IgA antibody responses and blocks infection in the M cell mucosal areas.

"It was done for polio," he said, "so it's not impossible to do it for HIV."

Yesterday, Dr. Poznansky unveiled an imaginative approach to AIDS therapy being explored in his lab. He made "fake" AIDS viruses that were mere shells, lacking internal components. Human cells readily absorbed these fakes, just as they absorb HIV, he said in an interview.

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