February 27, 2009

• Evolving DNA variations boost HIV's survival

• AIDS vaccine work must address 'escape' capacity

BIRMINGHAM, Ala. - The human immunodeficiency virus (HIV) adapts so well to the body's defense system that any successful AIDS vaccine must keep pace with the ever-changing immunological profile of the virus, according to researchers at the University of Alabama at Birmingham (UAB) and the University of Oxford in England.

A new study better describes HIV's ability to adapt by spelling out at least 14 different "escape mutations" that help keep the virus alive after it interacts genetically with immunity molecules that normally attack HIV.

The researchers analyzed genetic data from more than 2,800 HIV-infected patients on five continents. The findings are published online in the journal Nature.

"Key genetic regions of HIV introduced into individuals of different ancestry in different places have been evolving to a greater or lesser degree according to inherited factors controlling immune response," said Richard Kaslow, M.D., a professor in the UAB School of Public Health and a co-author of the study. "If HIV adapts differently in genetically distinct hosts, the challenge ahead in vaccine design is formidable," he said.

AVOIDING DESTRUCTION

The researchers looked at different DNA variations of HIV in conjunction with different forms of human leukocyte antigen (HLA), a group of molecules that orchestrate immune response. Normally HLA molecules present fragments of HIV proteins on the surface of infected cells to the immune system, acting as a signal for HIV destruction.

The Nature study shows just how efficiently the virus evolves escape mutations that help infected cells avoid destruction, Kaslow said. HLA genes themselves vary considerably across populations, most likely due to many biological and environmental factors that researchers are just beginning to understand.

The future of vaccine exploration will need to address the escape mutation capacity and identify new drug targets that work against an ever-changing HIV immunology landscape, said Philip Goulder, M.D., a professor of immunology at the University of Oxford and the study's senior author.

The study was a partnership between researchers at UAB; the University of Oxford; Kumamoto University in Japan; the James Martin 21st Century School in Oxford, England; Royal Perth Hospital and Murdoch University in Western Australia; Massachusetts General Hospital in Boston; Emory University in Atlanta; the International Medical Center of Japan in Tokyo; Germans Trias i Pujol University Hospital in Badalona, Spain; the University of West Indies in Bridgetown, Barbados; the Botswana-Harvard School of Public Health AIDS Initiative in Gaborone, Botswana; the Imperial College in London; the University of KwaZulu-Natal in Durban, South Africa; the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, Canada; the Howard Hughes Medical Institute in Chevy Chase, MD.

Funding came from the U.S. National Institutes of Health, the Wellcome Trust, the U.K. Medical Research Council, the U.K. National Institutes for Health Research Biomedical Research Centre Programme and the Mark and Lisa Schwartz Foundation.