A protein that is implicated in causing Alzheimer's disease may also play a role in the progression of HIV, researchers have found.
Apolipoprotein (apo) E4 isoform, responsible for neurodegeneration in Alzheimer's disease, cardiovascular disease, and stroke, may be a major risk factor in HIV progression, say researchers.
"The apoE4 protein is the greatest known genetic risk factor for Alzheimer's disease," said Gladstone Institutes president and study author Robert W. Mahley. "However, its role in infectious diseases has been less well-defined."
For the study, Dr. Mahley teamed up with Trevor Burt and Joseph M. McCune of the University of California, San Francisco, Brian Agan and Matthew Dolan of the Infectious Disease Clinical Research Program, and Sunil Ahuja of the University of Texas Health Science Centre at San Antonio to examine a large and well-characterized cohort of 1267 HIV-positive subjects of European and African American descent and 1132 ethnically matched seronegative controls.
Seronegative is a commonly used term to refer to the absence of antibodies to Rheumatoid factor or to HIV.
The team studied the interactions between apoE and HIV in tissue culture.
They found a much faster disease course and progression to death in patients with two copies of the apoE4 allele.
The corresponding apoE4 isoform promoted entry of HIV into cells. However, the apoE4 gene did not increase the incidence of HIV-associated dementia.
"A large body of evidence suggests that the amphipathic helical domains of apolipoproteins act as fusion inhibitors," said Dr. Mahley.
"We speculate that these domains in apoE inhibit HIV infection in a manner analogous to the clinical HIV fusion inhibitor Enfurvitide. Our findings suggest apoE4 is less efficient than apoE3 at inhibiting fusion of HIV to target cells," he added.
The findings from this study show that apoE is a determinant of the pathogenesis of HIV/AIDS.
The study is published in the new issue of the Proceedings of the National Academy of Sciences USA (PNAS).