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December 3, 2004

How Virus That Causes AIDS Spreads Following Oral Exposure

Topics: Medicine

The role of the oral mucosa in HIV infection is the topic of two separate but somewhat related research studies; one in which an animal model was used to trace how the virus may enter the body and spread after oral exposure, the other in which a mucosal adjuvant was utilized in nonhuman primates to identify an effective and safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine.

In Medical News Today, 04 Dec 2004. In a study conducted at the University of Texas Southwestern Medical Center at Dallas:

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.

Interestingly,  also reported recently -researchers at the University of Alabama in a study to determine the promise of a nontoxic mutant of cholera toxin (mCT; E112K) as a mucosal adjuvant in nonhuman primates appear to have identified an effective and safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine.

Reported in the J Immunol. 2004 Dec 1;173(11):6850-7, the article entitled, "A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates" discusses the use of HIV-1 gp120 nasally administered together with mCT E112K or native CT (nCT) as adjuvant on five to six occasions over a 6- to 8-wk period to groups of four rhesus macaques and alone to two monkeys that acted as controls. Macaques given nasal gp120 with either mCT E112K or nCT showed elevated gp120-specific IgG and IgA Ab responses with virus-neutralizing activity in both their plasma and mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab-forming cells in their mucosal and peripheral lymphoid tissues and of IL-4-producing Th2-type CD4-positive (CD4(+)) T cells than did controls.

Even though significant mucosal adjuvanticity was seen with both mCT E112K and nCT, neuronal damage was observed only in the nCT-treated, but not in the control or mCT E112K-treated groups. Their results showed that mCT E112K is an effective and safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine. Source...

Posted by Hyscience at December 3, 2004 10:23 PM

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