News Release

NSU research scientist leads group that discovered gene variants that delimit HIV-1 infection

New variants discovered in a genome-wide sequencing study of woman in Botswana

Reports and Proceedings

Nova Southeastern University

Dr. Stephen J. O'Brien with orphans in Botswana

image: Dr. Stephen J. O'Brien (back row, second from left) with orphans in Botswana view more 

Credit: Dr. Stephen J. O'Brien

Research Take-a-Ways:

  • This represents the first detailed study of a search for human genes that confer resistance/susceptibility to HIV infection and AIDS progression in an African population-Botswana.
    • Dozens of HIV-AIDS influencing genes have already been discovered (e.g. CCR5-∆32, which led to the first bona fide cure of HIV-AIDS), but all these genes were from European-American, European, or Caucasian ancestry.
  • This African study was made possible and facilitated by The Botswana-Harvard University AIDS Partnership, which was built in 1996 to provide surveillance, counselling, treatment, and research in the region of the world where AIDS in the most prolific.
  • The study revealed strong statistically robust implications of DNA variants in three human genes AP3B1-Chr-5; PTPRA-chr-20; NEO1-Chr-15, each of which is known to have a functional regulatory influence on AIDS pathogenesis.
  • These discoveries add to the promise of developing novel therapy targeted to the physiological pathways mediated with these three genes.


FORT LAUDERDALE/DAVIE, Fla. – HIV emerged from African chimpanzee transmission to humans in the first decades of the 20th century. The deadly AIDS disease was first detected among American gay men, hemophiliacs, transfusion blood recipients, and IV drug users sharing needles in the early 1980s. Since then, the rapid world-wide spread of HIV has claimed 37.2 million lives leaving some 38 million people living with HIV infection today.

Today, African AIDS comprises 65-70% of all HIV cases worldwide. In Africa, the HIV-1C strain, which has been suggested as more easily transmitted in heterosexual contact, is predominant. Although AIDS spread and transmission have been reduced by widespread dissemination of anti-retroviral therapies, the horror of AIDS continues, particularly in sub-Saharan Africa.

This study was led by Nova Southeastern University (NSU) Halmos College of Arts and Sciences professor and research scientist Stephen J. O’Brien, Ph.D., in collaboration with researchers at the Laboratory of Genomic Diversity at ITMO University, St Petersburg, Russia, Botswana-Harvard AIDS Institute, Gaborone Botswana, T. H. Chan School of Public Health, Harvard University, Boston, and Yale University, New Haven, and St. Petersburg State University.

Epidemiological variation in HIV acquisition, AIDS progression and therapy effectiveness has been attributed, in part, to endemic gene determinates. Studies in the past decades have discovered more than 50 human gene variants that confer relative sensitivity or resistance to AIDS. Nearly all these important studies involved American and European Caucasian patients in spite of the fact that sub-Saharan Africa is the epicenter of AIDS.

In 1996, author Max Essex and the President of Botswana established the Botswana Harvard AIDS Institute Partnership (BHP) in Gaborone Botswana to carry out training , surveillance and treatment of HIV-AIDS patients implementing research Virology, Molecular biology, immunology, genetics and epidemiology

In one of the largest studies to date of African people at risk for HIV infection, a group of 1,173 patients recruited by BHP were sequenced, genotyped, and analyzed to reveal three new common genetic DNA variants that influence whether one becomes infected and in American replication cohort studies the rate and AIDS defining disease by which infected individuals progressed to AIDS.

O’Brien and his team have pioneered the field of AIDS Restriction Gene discovery for 25 years, beginning when he led a Research Laboratory at the National Institutes of Health (1986-2012).

The research, published today in the Proceedings of the National Academy of Sciences, revealed three new human genes (AP3B1- Chr-5; PTPRA-chr-20; NEO1-Chr-15) with a marked influence on HIV acquisition.  Each gene variant was statistically significant in a Genome Wide Association Study -GWAS of 1.3-8.6 million single nucleotide polymorphism-SNPs.

The new study provides valuable insights into the genetic variants associated with HIV-1C infection and AIDS progression in sub-Saharan Africa, potentially paving the way for new therapies.

Each associated gene has been previously implicated functionally in one or more stages of AIDS pathogenesis and their association was replicated using independent American AIDS cohorts.

  • The AP3B1 variant is within the promotor regulatory region of the gene. AP3B1 is known to play a key role in HIV virion assembly and cell release and other steps in HIV production.
  • PRPRA encodes a membrane receptor and is a member of the tyrosine phosphatase family that is elevated in the CD4 T lymphocytes infected by HIV.
  • NEO1 encodes a cell surface protein that plays an important role in chronic inflammation induced by HIV infection.

A provocative aspect of the AP3B1 variant is that it encodes two alleles G and T, predicting TT, GT and GG genotypes. The Botswana population has a relatively high allele frequency of the G variant (MAF=0.38) relative to other world populations, yet no homozygous “GG” individuals were detected in Botswana. The GG genotype is also completely absent among 2500 people of all races studied to date, raising the prospect that the AP3B1 -GG genotype may be lethal genotype which does not survive embryogenesis. Further there are several described variants in the in the AP3B1 gene that cause Hermansky-Pudlak syndrome, a rare genetic disease affecting pigmentation and platelets that is sometimes fatal.

The study further describes the replication of 13 previously described AIDS resistance genes using the Botswana population cohort, increasing the confidence in the influence of each. The replication studies were facilitated by the GWATCH ( Genome Wide Association Tracks Chromosome Highway) cyber suite of programs that enhance GWAS data analyses, replication, and release.


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