United Press International - December 10, 1986

When he inoculated unaffected members of his laboratory flock with the filtered residue of tumors from diseased chickens, cancers identical to the malignancies of the afflicted birds developed.

Rous later described the first link between cancer and a virus, but what he had found was the first retrovirus, one in a complicated group of microbes now linked to cancer and acquired immune deficiency syndrome.

Two such viruses are associated with human cancers, and a third causes AIDS. Scientists are studying at least three others, two of which have been linked to AIDS. Another appears to cause no symptoms at all.

Researchers predict that other retroviruses will be discovered, possibly explaining the causes of rare malignancies and Third World diseases.

'Marvel of cooperation'

Dr. J. Michael Bishop, a virologist at the University of California, calls the life cycle of retroviruses "a marvel of cooperation between parasite and host."

Writing in an issue of Scientific American shortly after the 1980 discovery by Dr. Robert Gallo of HTLV-1, human T-cell leukemia-lymphoma virus, Bishop described the entire class of viruses as "unique in biology."

Scientists had long believed that in all living things genetic building blocks known as DNA had to be transcribed to RNA, another form of genetic material, and then to protein for reproduction to take place. With retroviruses, this process is reversed.

"Their RNA must be transcribed backward into DNA," Bishop said.

Retroviruses linked to human diseases include HTLV-1, HTLV-2 and HTLV-3, the virus that causes AIDS. HTLV-3 has since been renamed HIV-1, for human immunodeficiency virus.

Others recently discovered are AIDS viruses: LAV-2, discovered by French researchers, and another identified among West African AIDS patients in Sweden. Yet another, HTLV-4, bears many similarities to the AIDS virus but causes no apparent symptoms.

Mysterious origins

"HTLV-1 and HTLV-2 probably evolved millions of years ago," said Dr. David Golde, chief of hematology and oncology at UCLA and co-discoverer of HTLV-2. "But we don't know where on earth they came from."

Retroviruses mutate rapidly, changing part of their genes for adaptive purposes -- but "what they are adapting to is not always clear," Golde said. This characteristic poses problems for vaccine development.

Emerging data suggest there are specific areas of the world where certain retroviral infections are most common.

Clusters of HTLV-1 infections have been most prevalent in the southern islands of Japan and in the Caribbean.

Scientists at the National Cancer Institute in Bethesda, Md., say Japanese researchers estimate that as many as a million Japanese may have been exposed.

But studies in Japan also strongly suggest that many people who have been exposed to the virus and who develop antibodies against it never come down with a full-blown disease.

A cooperative study between the NCI and the University of the West Indies in Jamaica now is trying to estimate the number of Caribbean islanders who are antibody-positive for-HTLV 1.

"In Japan it is believed that women get it from men (during sex), but not the other way around," Golde explained. "But (they) also say that males get it in utero."

Sharp distinction

The clustering feature of-HTLV 1 exposure is so distinct in Japan that, whereas large sections of cities and villages have tested antibody-positive for the virus, people living in nearby areas show no evidence of exposure.

"This is the first well-documented tumor of man that is catching," Golde said of HTLV-1. "You can develop cancer if you receive the virus from other people."

Scientists say the cancer attributed to HTLV-1 is not easily transmitted. It appears mostly in families, it affects women more often than men and it usually does not occur before adulthood.

"Preliminary studies in the United States would indicate a prevalence significantly less than 1 percent," NCI researcher Dr. Stanley Weiss said.

A recent NCI study of black drug abusers in a section of the New York borough of Queens, where many AIDS cases have been reported, shows that the users carried antibodies to one or more retroviruses.

Seventy-three percent of the black drug users had the antibodies, compared with only 26 percent of white drug users who were exposed to at least one of the HTLV viruses.

Golde said that HTLV-1 and 2 are more closely related to each other genetically than to the AIDS virus, HTLV-3.

"Relatively little is known about HTLV-2, and differentiating (1 and 2) can be very difficult," Weiss said.

Golde said there is no endemic region for HTLV-2. Of the two cases treated at UCLA, the only factor the patients had in common was having once lived in Alaska.

"We still do not know if HTLV-2 is associated with a specific disease," said Golde.

Dr. Gary Norman of the Norris Cancer Center at the University of Southern California said the affinities of HTLV-1 and 2 for immune system cells are helping scientists learn more about the AIDS virus.

Bizarre effect

HTLV-1 and 2 share with the AIDS virus a bizarre capability of infecting T-cells of the immune system. T-cells, known more precisely as helper T-4 cells, help orchestrate the immune response when foreign matter invades the body.

But Norman noted that data continue to suggest that the AIDS virus has more in common with the class of animal retroviruses known as lentiviruses than it does to the two human retroviruses associated with cancer.

"The genetic sequences of HIV-1 and the visna virus of sheep are very much alike," said the AIDS researcher.

"This is not a cancer virus," said Dr. Jay Levy of UC San Francisco, the third scientist to isolate the AIDS virus. "HIV is in no way responsible for a disease that is similar to those caused by the cancer viruses.

Norman said that lentiviruses, first isolated in Iceland, do not infect people but have been linked to a sheep disease called scrapie.

"Visna means wasting in Icelandic, and that is one of the main features associated with such an infection," he said, referring to the progressive weight loss seen in AIDS patients.

"Some scientists call the AIDS virus a lentivirus because of the similarities," he said. "Lentiviruses are also slow viruses, and that means disease onset can occur years after infection." HTLV-1 and 2 and HIV-1 are slow viruses, too.

Insidious symptoms

Norman pointed out that lentiviruses are "nononcogenic," meaning that they do not cause cancer but are responsible for a number of insidious symptoms that gradually unfold.

Scientists have not yet determined what induces a latent lentivirus to begin replicating inside a cell in which it essentially had been dormant.

Researchers have identified more than 85 retroviruses -- some of them harmless to host animals -- and say they appear to be widespread throughout vertebrate species, Norman said.

Dr. Max Essex, a veterinarian and chairman of cancer biology at Harvard University School of Public Health, has long suggested that the AIDS virus probably had animal origins.

Many initial cases of the disease were seen among animal handlers in central Africa -- the epicenter of AIDS cases on that continent -- where monkeys were captured for zoos and research.

Michael Nine, a spokesman for the World Health Organization in Washington, said the international agency now estimates that 50,000 Africans have died of AIDS since 1980 and five million more are carrying antibodies.

CAPTION: MAP Retroviral Infections Worldwide

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