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BYU researchers take look at how HIV adapts

PROVO — A set of twins, a failed vaccine and a protein "stop sign" have led three research teams conducting different studies at BYU to increased understanding of how HIV changes and produces more virus.

A number of years ago, identical twin baby boys received a tainted transfusion and both became HIV-positive. Now, one of the twins has a near-normal immune system and pretty good health, while the other boy is five years behind him on the growth chart and has experienced a number of complications.

That provocative difference became the foundation of one of the three studies, as researchers led by Brigham Young University biology department chairman Keith Crandall studied how the virus changed in each twin. They were joined in the study by scientists at the National Cancer Institute.

The second study focused on an HIV vaccine Thailand was trying to develop that didn't prove effective. What Crandall and other researchers found there, though, was a population that had been subjected to regular blood draws, including some before and after they contracted HIV. Those samples afforded the researchers another look into how the virus evolved.

The third study, by the Department of Chemistry and Biochemistry chairman Greg Burton, colleagues from BYU and the University of Colorado Health Sciences and student Xueyuan Zhou, confirmed an earlier report that a naturally occurring protein prevents HIV from multiplying. But unlike that earlier research, they were also able to explain how the protein works, not just what happens.

Burton said the study that looked at the effect of the protein a-1-antitrypsin was a follow up to earlier research that found the protein could inhibit HIV. AAT, as the protein is called, has already been approved for use in treating chronic obstructive pulmonary disease. The scientists explained that "at the right levels, AAT alters the activation of a separate protein that HIV needs to transcribe its genetic code in the replication process. Without the needed protein, HIV doesn't produce more virus."

"The importance of this study is that we moved ahead from earlier research. The effect was known, but we showed the mechanism," he said.

In the Thailand study, researchers realized that the virus' evolution was not being hampered by the so-called vaccine. HIV vaccine-wise, Crandall said, "it suggests we're back to square one." Experts are continuing to work on a vaccine. Researchers also found in Thailand a close HIV-infected community. So close, in fact, that they could spot subjects who may have shared the same needle during drug use, because the virus was identical. That closeness is actually detrimental to vaccine trials because researchers must have diversity to determine if a vaccine works.

As for the twins, Crandall said there are competing theories about the differences in their clinical outcomes. One theory is that natural selection drives it, so the results should be similar. The other holds that random genetics plays a role and it therefore cannot be predicted.

"I think the HIV community is still split in terms of how to pursue treatment against HIV infection," Crandall said. "There is a strong camp that thinks vaccine is still the way to go. We need to do more intelligent vaccine design," carefully considering everything they've learned in other attempts to create a vaccine that works.

"Others say no way," Crandall added. "The focus needs to be on drug therapy. But the virus tends to hide out in places where drugs can't get to them."

That's one of the big tasks Burton's research team is thinking about. They're looking or ways to flush the virus out of the pockets where they hide. "That seems to be at the moment the most successful approach," Crandall said. "More headway is being made in that area and good teams are pursuing it.

The twin study was published in the journal BMC Evolutionary Biology. The Thailand-related study was published in the scientific journal PLoS One. And Burton's research is published in the Journal of Immunology.