Mar. 24, 1998 DALLAS * March 20, 1998 ** Researchers at UT Southwestern Medical Center at Dallas are offering the first plausible molecular explanation of why the human immunodeficiency virus (HIV) is more easily transmitted to or from people with syphilis. This knowledge could lead to treatments to slow progression of the disease.
"Syphilis also is a chronic, systemic illness in which the bacteria migrate rather freely throughout the body causing inflammation at numerous sites," said Dr. Michael Norgard, acting chairman of microbiology and senior author of the article in the April Journal of Infectious Diseases. "By extrapolation of what likely occurs in the genital ulcers caused by syphilis, systemic levels of bacteria from that disease actually may activate immune cells throughout the body. Higher levels of HIV could interfere with efficacy of HIV treatment and even accelerate the course of AIDS."
In a collaborative effort, scientists in the laboratories of Norgard and professors of internal medicine and microbiology Drs. Richard Gaynor and Justin Radolf looked at immune cells in laboratory dishes to determine if the syphilis bacterium or its membrane lipoproteins could trigger latent HIV gene expression. HIV is the virus that causes AIDS. The lipoproteins are fatty acid-containing molecules that serve a variety of functions at the cell surface. Researchers were interested in whether gene expression appeared in the primary genital ulcers, or chancres, of syphilis.
"We think the lipoproteins, a class of cell-membrane proteins in the syphilis bacterium, predominately cause the inflammatory processes that typify the disease," said Norgard, holder of the Roy and Christine Sturgis Chair in Biomedical Research.
"What is implied in our findings is that syphilis may predispose a person toward more rapid progression of HIV disease," he said.
No one previously studied whether syphilis speeds progression of HIV into AIDS. It is known that patients with chronic secondary infections associated with AIDS exhibit higher HIV levels because of the constant stimulation of the body's immune system.
"The research is especially significant because we joined two areas of molecular biology, HIV and syphilis, so that we could develop experimental models and determine more fully the association between the two diseases," Radolf said. "It was truly a joint effort by all the investigators involved."
According to the Centers for Disease Control and Prevention (CDC), people with syphilis are two to five times more likely to transmit or contract HIV than individuals not infected with a sexually transmitted disease. Epidemiological studies have attributed this to the open sores on the genitals or oral cavities of people with syphilis
Future research could involve a clinical study to find out if patients infected with both HIV and syphilis have higher levels of the virus before they are treated for the bacterium with penicillin. Identifying people with syphilis is more difficult than curing them because many don't seek help due to fear, lack of money or absence of convenient medical facilities.
Syphilis has a long progression and can lay dormant for years if untreated. Potentially fatal, syphilis can lead to blindness, impotence or insanity if the bacterium enters the nervous system. But the disease usually is easily treated and cured with an intramuscular shot of a slow-acting penicillin.
Though cases of syphilis in the United States have dropped steadily over the past few years, it remains a major public-health problem. CDC reports that the disease is more prevalent among blacks, and the region of the country showing the highest rate of the disease, the South, is also the area with the largest number of heterosexually transmitted cases of HIV. According to Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, the number of HIV cases transmitted through male-female sexual contact in the United States increased from 4.8 percent in 1988 to 20.3 percent last year. About 860,000 U.S. residents have the AIDS virus.
"Our research is a first step toward understanding the molecular events that may trigger activation of the immune cells that support HIV replication in the setting of syphilis co-infection," Norgard said.
Also involved in the study were: Dr. Sue Ann Theus, assistant instructor of microbiology, and Dr. David Harrich, former instructor of internal medicine. Gaynor, chief of hematology and oncology, chief of molecular virology and holder of the Andrea L. Simmons Distinguished Chair in Cancer Virology, also is acting director of the Harold C. Simmons Comprehensive Cancer Center.
The National Institutes of Health, the Robert A. Welch Foundation, the Department of Veterans Affairs and the American Heart Association funded the research.
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