Mayo researchers observe genetic fusion of human, animal cells -may help explain origin of AIDS

Mayo Clinic genomics researchers are the first to demonstrate that mixing of genetic material can occur naturally, in a living body. The researchers have discovered conditions in which pig cells and human cells can fuse together in the body to yield hybrid cells that contain genetic material from both species and carry a swine virus similar to HIV (the virus that causes AIDS) that can infect normal human cells.

While the research does not answer the question of whether this infection can cause actual disease in humans, it does provide scientists with a new way to understand how viral infections can pass from animals to humans.

“What we found was completely unexpected,” says Jeffrey Platt, M.D., director of the Mayo Clinic Transplantation Biology Program. “This observation helps explain how a retrovirus can jump from one species to another — and that may speed discovery about the origin of diseases such as AIDS and SARS. The discovery also may help explain how cells in the circulation may become part of the solid tissue.” The Mayo Clinic research appears in the online Express edition of the FASEB Journal. (www.fasebj.org) published by the Federation of American Societies for Experimental Biology. The print article will appear in the March issue of the journal (volume 18, issue 3).

Known as “zoonosis or zoonotic infection,” the movement of an infectious agent between animals and humans is of intense interest to those who study public health, infectious diseases, immunology and transplantation. Some viruses, such as influenza, are well known to pass from one species to another. Other viruses do not appear to easily cross species — and yet do so under rare, unknown circumstances.

Scientists want to know how and why viruses cross species because zoonosis may underlie some of the most devastating diseases. For example, researchers have long believed the HIV virus that causes AIDS in humans originated in wild primate populations and crossed into humans a few decades ago. More recently, scientists have thought that the coronavirus responsible for SARS crossed into humans from wild animals such as the palm civet cats of Asia.

A Possible New Model for Understanding AIDS

In the research reported today, Mayo Clinic investigators implanted human blood stem cells into fetal pigs. The pigs look and behave like normal pigs. But cellular analysis shows they have some human blood cells, as well as some cells that are hybrids — part human, part pig — in their blood, and in some of their organs. Molecular examination shows the hybrid cells have one nucleus with genetic materials from both the human and the pig. Importantly, the hybrid cells were found to have the porcine endogenous retrovirus, a distant cousin of HIV, and to be able to transmit that virus to uninfected human cells.

Background: What Led to This Research?

The Mayo Clinic research team has long been interested — and is a world leader — in xenotransplantation (ZEE-no-transplantation). This is an experimental field within transplant biology in which specially bred and raised pigs might eventually become donors for humans to meet the drastic shortage of suitable donor organs. Worldwide, thousands of people suffer failure of such organs as the liver, kidney, heart, lung and pancreas and require transplants — but face death due to shortage of suitable donor organs. Xenotransplantation is just one experimental avenue being explored as a way to meet this shortage.

One central concern of investigators is the potential for zoonotic transmission of disease when an animal organ is surgically implanted into a human. One virus of concern is the porcine endogenous retrovirus, which is present in all pigs. The current research provided two important discoveries: the virus can pass to human cells in the body and it can be infectious. But whether it can actually cause disease in humans is not yet known.

Says Dr. Platt, “Perhaps this model or one like it can help to answer this question. And perhaps similar models can be used to identify other viruses of concern before outbreaks occur in humans.”

The Next Step

The experiment has been repeated a number of times, but it needs to be further scrutinized. “We’re really working hard to figure out how it happened, and what implications it might have beyond the transmission of the one virus we studied,” Dr. Platt says.

The research was conducted in the Transplantation Biology Program at Mayo Clinic. In addition to Dr. Platt, the research team consisted of Brenda Ogle, Ph.D., first author of the article, and Marilia Cascalho, M.D., Ph.D., who was in charge of genetics in the study.

Mayo Clinic conducts research in medical genomics in order to improve patient care. Its scientists and clinical investigators strive to turn laboratory discoveries into beneficial therapies as quickly as possible.