Animal model helps explain how AIDS virus spreads throughout the body following oral exposure

Researchers at UT Southwestern Medical Center at Dallas have utilized an animal model to trace how the virus that causes AIDS in humans may enter and spread throughout the body following an oral exposure.

By innoculating monkeys with SIV, the simian version of HIV, scientists traced which tissues in the mouth and digestive tract were infected during the first week. Furthermore, they traced which organs and lymph nodes were first infected and uncovered likely routes of infection. The findings are published in today's issue of the journal AIDS.

"This is the first study to assess which tissues had SIV nucleic acid at the earliest times following an oral infection," said Dr. Donald Sodora, senior author of the paper.

Oral transmission of HIV is problematic, especially in developing countries where bottle-feeding infants is not practical. Up to one third of newborns may become infected with the virus that causes AIDS as a result of breastfeeding from an infected mother. There is no evidence that saliva transmits the virus from one person to another. However, oral exposure to the virus through breast milk or semen (during sexual contact) may result in a higher number of infections than originally thought.

The new findings better define early infection in the monkey model, which researchers say they hope will lead to a future vaccine. The animal studies were conducted at the California National Primate Center at the University of California, Davis in collaboration with Dr. Marta Marthas.

"Our goal is to assist in the design of vaccines by providing a more thorough understanding of the early events following oral infection," said Dr. Sodora, assistant professor of internal medicine and microbiology.

In the study, monkeys were infected with SIV administered onto the cheek pouch of the rhesus macaque, likely coming into contact with the oral mucosa and tonsils before being swallowed. Studying the monkeys after exposure, researchers uncovered the sites of transmission and a rapid spread of the virus to surrounding lymphoid tissues. Likely sites of infection included soft tissue in the mouth, esophagus and tonsils.

Further examination of the digestive tract showed that SIV was not present in tissues below the esophagus until four days post-infection, indicating that the stomach acids probably prevented the virus from entering through the stomach or intestines.

"It is clear from our study that the oral and esophageal mucosa and the tonsils are likely to be the most important sites of viral entry," Dr. Sodora said. "These tissues should be a major focus of any additional studies of HIV or SIV oral transmission."

At one day following oral exposure, the first lymph nodes infected were closest to the head and neck. Four days after infection, the virus could be detected in nearly all tissues.

"The ability of virally infected cells to spread so quickly from the site of infection to numerous lymph nodes throughout the body was surprising," Dr. Sodora said.

Researchers further examined the route by which cells carried SIV throughout the bodies of infected monkeys and found that T-cells and macrophages likely played key roles in disseminating the virus.

Because SIV spreads so rapidly throughout the bodies of infected monkeys, it may help to explain why antiviral therapies can effectively protect a monkey or HIV infection of humans only if they are given within hours of exposure to the virus.

Researchers hope the study further identifies one of the major problems facing the formulation of a vaccine: any vaccine needs to overcome the rapid spread of the virus from the site of infections to tissues throughout the body.

The study was funded by the National Institutes of Health Institute of Dental and Craniofacial Research.

Other UT Southwestern authors include graduate students Jeffrey Milush and David Kosub; laboratory manager Frederick Scott; and research associate Aneta Wozniakowski.