Newsday - May 31, 2001
Laurie Garrett, Staff Writer

And that has some biologists worried about the insidious next pathogen that may surface, taking advantage of such an enormous pool of people with compromised immune systems.

"I can envisage other horror scenarios," says Dr. Robin Weiss of the Wohl Virion Centre at University College in London. "Where 10 percent or more of the population is immunocompromised due to HIV infection, just imagine how previously rare opportunistic infections could rapidly evolve to become novel human-to-human pathogens."

Weiss recently authored a forecast for the British science journal Nature in which he suggested: "Microbes that are poorly adapted for human infection could become well adjusted, first to the immunodeficient host and eventually to immunocompetent humans, provided they learn the tricks of human-to-human transmission. This could include free-living microbes from the environment ... as well as microbes and parasites from other animal sources."

Bacteria could become increasingly drug resistant.

Floating pieces of "harmless" genetic material, which are common now, could take on lethal forms. And, Weiss predicts, even if HIV comes under control by immunization, "new diseases may roam former HIV land."

Such speculation may seem apocryphal, except for two points: First, the explosion of HIV is occurring at the same time as societies of the wealthy world are aging. With age, most people's immune systems deteriorate, rendering them fatally vulnerable to infections such as the flu.

And such events already have occurred with HIV. Several diseases have taken advantage of the immune-compromised AIDS populations, causing not only unusual ailments in HIV-positive individuals but also communitywide outbreaks. These include cryptosporidiosis (an intestinal disease passed in contaminated water), multidrug- resistant tuberculosis, HHV-8 (a cancer-causing virus), Herpes simplex virus, vaccine-associated viruses and bacteria, Mycobactrium avium (a bird form of tuberculosis), toxoplasmosis, bird viruses and farm animal parasites.

"The one I worry about is what it's going to do to TB on a large scale," says Dr. David Ho, director of the Aaron Diamond AIDS Research Center in Manhattan. "When I went to rural areas in China, you could just go and track the HIV epidemic by TB. And that could really take off in Asia as the epidemic blossoms. Of the ones we know about, that's the one that's so frightening."

And what about the ones we don't know about?

Scientists recently completed a rough sequence of the entire human genome. And among the surprises was discovery that 8 percent of all the genes in human beings are HERVs-Human Endogenous Retroviruses. Like HIV, there are dozens of retroviruses that have infected human beings, or our ancestor species, says virologist John Coffin of Tufts University in Boston. The HERVs got into human DNA thousands, even millions, of years ago, and have passed from one generation to the next. In some cases they have come to perform useful functions in human biology.

Weiss has asked whether such viruses, or viral fragments, could emerge again, popping out of our DNA to cause disease.

Coffin's laboratory is dedicated to answering such questions. Last week, his team announced at the Cold Spring Harbor Laboratory's annual retrovirus meeting the discovery of 26 HERVs in human DNA, many of which appeared to date to pre-human ancestor species. And, in a first of its kind, Coffin's laboratory successfully resurrected one such virus from its millions-of-years-long sleep inside the DNA of mice.

"It's like pulling dinosaur DNA from amber," Coffin said. "You know, 'Jurassic Park,' " a reference to the Michael Crichton book.

Coffin's lab identified a genetic sequence in mouse DNA that looked like an ancient retrovirus. The lab cloned it, added a few missing bits of genetic material, and, sure enough, out popped a fully infectious virus. The question remains: Could such events happen in nature?

Finally, Weiss and his worrying colleagues wonder whether HIV, itself, might change in dangerous ways.

"This virus mutates a nucleotide every time it replicates, and it replicates every eight hours," explains Dr. Jeffrey Laurence of Cornell University Medical College in Manhattan. "One of these days, by random mutation, we might get something new."

Using new methods of measuring HIV mutation rates, Carrie Dykes and her colleagues from Rochester University Medical Center announced at the Cold Spring Harbor meeting that the virus may actually change itself far more rapidly than that, both through mutations and by combining bits of one HIV strain with bits from another. Every increment of HIV's genetic material mutates, on average, two times out of each 1,000 rounds of viral replication. That's a complicated way of saying HIV may, if the Dykes results hold up, be changing itself 10 times more frequently than previously thought.

Such observations prompt Weiss to say that "one nightmare scenario for us would he if HIV were to change its mode of transmission ... Can we be sure that it is beyond the ingenuity of HIV to travel aboard the mouthparts during interrupted feeding of common bugs? If Yersinia petstis can switch from flea-borne bubonic plague to the air- borne pulmonary form of the disease, could HIV also sample new transmission dynamics-adding saliva, aerosol or [insect] vectors to the sex and blood it already enjoys?"
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