Identity crises in AIDS virus studies?

Identity crises in AIDS virus studies?

With so much still unknown about AIDS, each additional piece of information is welcome. But data must be gathered carefully and critically, according to recent reports illustrating the potential pitfalls of virus identification. In two studies released last week, one group of researchers suggests that the most virulent immunodeficiency viruses may escape isolation and detection by current laboratory methods, while another presents evidence that a virus isolate thought to be HIV-2 is actually a contaminant from monkeys.

By studying a virus responsible for feline leukemia, researchers at the Harvard School of Public Health in Boston and at Colorado State University in Fort Collins found that procedures used to separate viruses may fail to isolate "acutely pathogenic" (disease-producing) virus strains while selecting for less virulent viruses. The scientists, hoping to develop an animal model for AIDS, have been focusing on a naturally occurring virus strain they call FeLV-FAIDS, whih also causes a fatal feline immunodeficiency syndrome.

In 1986, when the scientists announced that they had found the feline immunodeficiency virus, they also reported that there were several types of FeLV in the tissues of affected cats. Now, after cloning and DNA sequencing these different viruses, they write in the Feb. 19 SCIENCE that the feline viruses causing the immunodeficiency syndrome are "replication defective," or unable to multiply well in vitro -- suggesting that researchers must take the viruses directly from tissues in order to identify all involved. The authors say that this diversity also occurs among viruses linked to human and monkey AIDS, and that the current approach of growing viruses in vitro before study may not isolate the more important strains.

In the second study, it apparently was a problem of too many virus isolates rather than too few. Reporting in the Feb. 18 NATURE, researchers at the New England Regional Primate Research Center in Southborough, Mass., say they have "strong evidence" to confirm scientists' suspicions that a virus used at the Harvard school of Public Health as an HIV-2 isolate is actually a simian immunodeficiency virus (SIV) from rhesus macaque monkeys.

Thought to be associated with an AIDS-like condition primarily found in West Africa, HIV-2 apparently is less virulent than HIV-1, but is considered an important key to understanding the spread of AIDS. Trying to sort out the various viruses somehow affiliated with AIDS, however, can be confusing, as the current report suggests.

The Southborough group isolated the virus the scientists called SIV.sub.MAC from captive macaques in 1985. Within two years, the Harvard group and a group of French scientists had reported the isolation from humans of HTLV-IV and LAV-2 respectively, both later renamed HIV-2. The Harvard researchers had also isolated a virus from green monkeys that they called STLV-III.sub.AGM., and both the green monkey virus and HTLV-IV were used in subsequent studies in Africa. But the Southborough group's comparison of DNA sequences from HTLV-IV and STLV-III.sub.AGM now shows that the two viruses are actually a variant of SIV.sub.MAC that probably contaminated Harvard's cultures.

This mistaken identity is readily acknowledged in an accompanying reply from Harvard's Myron Essex and Phyllis Kanki. They say, however, that -- because SIV and HIV-2 can be used "interchangeably" in screening tests -- results from epidemiology studies based on what have proved to be lab contaminants "remain as originally stated." Commenting in the same issue of NATURE, Carel Mulder of the University of Massachusetts Medical School in Worcester says that "this episode should serve as a strong warning for all virologists working with multiple isolates."