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Researchers Discover that Sheep Need Retroviruses for Reproduction

13.09.2006

A team of scientists from Texas A&M University and The University of Glasgow Veterinary School in Scotland has discovered that naturally occurring endogenous retroviruses are required for pregnancy in sheep.

In particular, a class of endogenous retroviruses, known as endogenous retroviruses related to Jaagsiekte sheep retrovirus or enJSRVs, are critical during the early phase of pregnancy when the placenta begins to develop.

Retroviruses, such as human immunodeficiency virus or HIV, are one class of viruses. They are best known for their ability to cause diseases, said Dr. Thomas Spencer, a reproductive biologist with the Texas Agricultural Experiment Station and Texas A&M University.

Findings published Sept. 11 in the Proceedings of the National Academy of Sciences demonstrate enJSRVs are essential for the development of the placenta in sheep.

Retroviruses are unique for their ability to permanently insert their genetic material into the DNA of host cells, he said. During evolution of mammals, some retroviruses infected the germline (cells of the ovary and testis that have genetic material that are passed to their offspring) of the host, which is then inherited by their children. These retroviruses, known as endogenous retroviruses, are present in the genome of all mammals, including humans. Consequently, endogenous retroviruses can be considered remnants of ancient retroviral infections, Spencer said.

Many scientists believed these endogenous retroviruses were junk DNA, he said.

"Indeed, these endogenous retroviruses are usually harmless and generally contain mutations that prevent them from producing infectious retroviruses," he said.

However, several endogenous retroviruses appear to provide protection from infection and are involved in reproduction. For instance, the exogenous Jaagsiekte Sheep Retrovirus or JSRV causes lung tumors in sheep and led to the death of Dolly, the world's first mammal cloned from an adult cell.

The idea that endogenous retroviruses are important for reproduction in mammals has been around for about 30 years, Spencer said. Studies in cultured cells have shown that a protein of a human endogenous retrovirus might have a role in development of the human placenta.

The team blocked expression of the envelope of the enJSRVs using morpholino antisense oligonucleotides, which inhibit translation of specific messenger RNA. When production of the envelope protein was blocked in the early placenta, the growth of the placenta was reduced and a certain cell type, termed giant binucleate cells, did not develop.

The result was that embryos could not implant and the sheep miscarried, Spencer said.

Miscarriage is a serious medical problem for all mammals, including humans.

"Our research supports the idea that endogenous retroviruses shaped the evolution of the placenta in mammals and then became indispensable for pregnancy, and thus may be why they are expressed in the placenta of many mammals," he said.

Further, Palmarini said, "The enJSRVs arose from ancient infections of small ruminants during their evolution," said Dr. Massimo Palmarini, a virologist at The University of Glasgow Veterinary School. "This infection was beneficial to the host and was then positively selected for during evolution. In other words, animals with enJSRVs were better equipped than those without. Therefore, enJSRVs became a permanent part of the sheep genome and, in these days, sheep can't do without them."

The research team is trying to determine exactly how enJSRVs function in development of the sheep placenta. Their results should have implications for both human health and animal production.

The team was led by Spencer and Palmarini. Team members are Kathrin Dunlap, Robert Burghardt, Kanako Hayashi and Jennifer Farmer at Texas A&M, and Mariana Varela at The University of Glasgow Veterinary School.

The work of the research team has been funded by the Wellcome Trust in the United Kingdom and the National Institutes of Health in the U.S.