The New York Times - July 20, 1984
Lawrence K. Altman

The gene discovery has led the scientists at Harvard and the National Institutes of Health to theorize about a new molecular biological mechanism to explain how a group of HTLV viruses, or human T-cell lymphotropic viruses, can alter an infected cell's machinery, allowing the virus to be produced efficiently and to change the cell's growth properties.

The scientists also described structural features of the viral genes that they said offered insights into the function of the viruses that could be important for diagnosis, prevention and therapy of cancers and other diseases.

"It is a major scientific discovery" in explaining how cancer could be caused by viruses under some circumstances, Dr. William A. Haseltine, the cancer researcher who headed the team, said in an interview. He elaborated on findings that are described in three papers published in the July 27 issue of the journal Science, which was released yesterday.

Need for Testing

Although the research "gives us hope and a path to follow which we didn't have before," such therapies and preventions would take years to develop and would require extensive testing in animals before being tried on humans, Dr. Haseltine said. Moreover, he cautioned, "It doesn't mean that such developments are possible."

Another virologist not connected with the reports called the new findings "very significant" and also cautioned that the proposed practical benefits were scientifically speculative and would take many years to bring about.

Nevertheless, the findings have led the scientists to devise a new scheme to make vaccines against the human diseases caused by HTLV retroviruses. The scheme involves a concept that scientists call the "screwed up virus" approach in which sections of the virus can be changed in such a way as to cripple their ability to cause disease but still stimulate the body to form protective antibodies.

The new concept is important because previous efforts to make vaccines against experimental retroviruses have at best had limited success.

There are three types of HTLV viruses, designated HTLV-1, 2 and 3. Type 1 causes a rare type of leukemia. Type 2 has been linked to another rare type of leukemia but the finding is less certain than type 1 because type 2 has been reported in only one or two patients.

A third type has been implicated as the cause of AIDS and it destroys a blood cell known as the T-4 lymphocyte, leading to potentially lethal infections with microorganisms that ordinarily do not harm unaffected people. The T-4 cell, which is destroyed in AIDS, has been called a master gland of the immune system because it produces hormones that regulate immune functions. French and U.S. Discoveries

American researchers at the National Cancer Institute call this virus HTLV-3; French researchers at the Pasteur Institute in Paris call it LAV. The researchers have said they believe the viruses are the same.

Scientists know that most viruses cause infection by attaching themselves to cells and then entering to cause damage. However, scientists have been baffled by how some members of one family of viruses can cause cancer, and another viral family member can destroy cells such as in AIDS. Cancer is the result of an uncontrolled growth of cells and AIDS results from the destruction of the T-4 lymphocyte.

In their research at the Dana-Farber Cancer Institute in Boston, Dr. Haseltine's team documented a new phenomenon: the ability of HTLV viruses to reprogram the part of an infected cell's machinery so that the viruses can be produced efficiently.

That discovery has led the scientists to begin testing their theory that viral proteins produced by the leukemia- causing types of HTLV turn on genes that make infected cells grow, whereas the AIDS virus either turns off such genes or turns on genes that cause the cells to stop growing.

To begin to understand how the virus changes the infected cell's decoding program, the researchers studied similarities and differences in the molecular structure of the HTLV-1 and HTLV- 2 viruses.

Also, in collaboration with other researchers at Harvard and at the National Cancer Institute, Dr. Haseltine's team determined the structure of an area of the virus known as the surface envelope to produce antigens. These foreign substances lead to the production of protective antibodies. Role in Infection

The surface envelope plays a key role in allowing the virus to enter human cells to infect them. The surface envelope protein is also regarded as a foreign substance that stimulates the body to produce protective antibodies against the virus.

By testing the ability of the protein contained in the surface envelope or fragments of it to produce antibodies, the scientists theorize they could develop schemes to produce vaccines against the rare types of leukemia and AIDS.

They also theorized that they could create a different type of vaccine based on a virus that was missing a section known as LOR, for long open reading frame. Such viruses ought to be crippled in their ability to cause disease but still should be able to grow slowly and induce protection, the researchers said.

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