Food fungus worsens African AIDS epidemic

I keep coming across factors that, while not directly related to the nature of the human immunodeficiency virus (HIV), are nonetheless driving the African AIDS epidemic.

Take the recent news about a study from the School of Public Health, which found that a type of fungus coating much of the stored corn, rice and nuts in many African and Asian countries may be weakening immune systems and encouraging HIV infection.

Kept in sacks piled in warehouses, food stores in countries near the equator are often contaminated by Aspergillus flavus and A. parasiticus, fungi that produce a toxic substance called aflatoxin.

About 4.5 billion people worldwide are exposed to aflatoxin at unsafe levels, and chronic exposure has been linked to liver damage and related cancers.

Work by Pauline Jolly, Ph.D., professor in the Department of Epidemiology within the UAB School of Public Health, argues that aflatoxin exposure may be taking an even greater toll in areas where millions are infected with HIV. The research team divided 314 HIV-positive people from Kamasi, Ghana, into four groups based on their level of aflatoxin exposure.  The team found that those in the highest exposure group were 2.6 times more likely to have a high HIV viral load than those in the lowest exposure group. Higher viral load translates into higher rates of HIV transmission. For information, please see our news release and related coverage by the New York Times.

Along the lines of non-viral factors worsening the AIDS epidemic was another study published this past August, also from the School of Public Health. Janet Turan, Ph.D., associate professor in the Department of Health Care Organization and Policy, and her team found that the fear of being labeled HIV-positive was strong enough to keep mothers from Kenya from having their babies in health-care facilities. Communities there have come to see clinics and skilled care as mostly for HIV-positive women, and HIV often is linked to promiscuity in the eyes of a woman's family.

In Nyanza, Kenya, a region where one in five pregnant women is HIV-positive, skilled care during pregnancy and birth increases the likelihood that those infected will receive antiretroviral drugs that prevent the passing of HIV from mother to child.

It just seems like Africa can’t get a break.

More troubling yet, the search for solutions to the epidemic's many contributors is not accelerating in the age of research budget cuts. The grants that paid for Jolly's research into the aflatoxin and HIV have ended, leaving her unable to pay for a full data analysis of the consequences of combination exposure on sets of immune cells. She does not know where her next round of funding will come from.

“A fungal contribution to HIV transmission will only be proved once and for all by larger randomized studies for which there now is no funding," Jolly said. "The scientific and world-health communities need to decide soon whether or not this question is worth answering.”

Genomic marathon is worth it

Imagine a project so vast that you could work on it for 20 years, spend $4 billion and still have only just moved it off the starting line. Would you ever finish?

Those questions have for years faced the massive effort to understand human genetic material. The Human Genome Project cost roughly $3.8 billion from 1998 to 2003, and a central message afterward was that “we have but scratched the surface in our understanding.” The ENCODE project picked up where the Human Genome Project left off in 2003, seeking to understand which bits of the genome have an active role in human biology despite their not being genes.

While the 20,000 or genes discovered during the Human Genome Project are a central part of the “blueprint for human biology,” ENCODE has helped to confirm that genes represent less than 2 percent of the genome. Genes, it turns out, are surrounded by vast stretches of code, some of which control when, where and how genes turn on and off.

Teams of ENCODE researchers recently published 30 research papers that represent an early round of results, according to an article in the journal Nature. But how far have we come after adding ENCODE’s seven years and $185 million to our monumental investment in the Human Genome Project?

We asked Michelle Amaral, Ph.D., study navigator in the UAB School of Medicine’s Department of Genetics, for her perspective as part of the next generation of genomic researchers. She thinks ENCODE is worth the investment based on its contributions to date and its potential.

In part thanks to ENCODE, doctors today can assess the impact of small variations in a person’s genome on several diseases, and tailor their treatment accordingly. Amaral mentioned Bruce Korf, M.D., Ph.D., chair of the Department of Genetics, as an example of a UAB genomics researcher whose work is already contributing to both personalized medicine and advances against rare diseases.

What’s taking so long? 

More than 400 ENCODE scientists had completed roughly 1,600 experiments on 150 different cell types in time for the recent ENCODE publications. Despite this frenzy of activity, however, efforts to map the function of the entire human genome are about halfway there, with an in-depth description of the genome’s function just 10 percent complete, according to experts quoted in the Nature article.

“Each person’s DNA code consists of about 3 billion chemical units,” says Amaral in way of explaining the “slow” pace. “Sorting them into genes, gene triggers and gene networks is like trying to piece a foreign alphabet into sentences, stories and libraries of stories, and without knowing the grammar rules.”

From another angle, the ENCODE consortium has already done great things. It has assigned a rough function to about 80 percent of the human genome, although critics argue some of this functional DNA is really junk. It has identified the DNA binding sites for about 120 transcription factors, proteins that control when genes switch on and off to express proteins. And it has mapped genome regions “carpeted” with molecules called methyl groups that confer still more precise control over gene expression.

These mechanisms for genetic fine-tuning may explain why humans are so complex, despite having fewer genes than grapes.

Furthermore, ENCODE has identified thousands of points on the genome where a single-letter (single-molecule) difference in the code contributes to a genetic disease, with 90 percent of them falling outside of genes.

Those interested in learning more should visit the ENCODE project website, the National Human Genome Research Institute ENCODE site, or follow ENCODE on Facebook or Twitter.

UAB genomics retreat

UAB faculty, trainees and students will have a chance to learn more about the field, share work and network at the UAB Genomic Medicine Retreat on Tuesday, Sept. 25. The event will be held in UAB’s Alumni Auditorium.

UAB speakers will include Drs. Korf and Amaral, as well as Lynn Holt, program director for the Genetic Counseling Program, Elliot Lefkowitz, Ph.D., associate professor in Department of Microbiology, and Jonas Almeida, professor in the Department of Pathology. Dan Roden, M.D., professor of Medicine and Pharmacology at Vanderbilt University will also speak. Registration is required and may be completed here.

The list of retreat sponsors reveals the power of the genomics collaboration under way at UAB: the Center for Clinical and Translational Science, Heflin Center for Genomic Science and the Comprehensive Cancer Center.