Study published in the Journal of Neuroscience compared HIV clade B, which leads more often to dementia, to clade C.

Scientists report that they have clarified how two major variants of HIV differ in their ability to cause neurologic complications. The researchers noted earlier studies showing that people with AIDS in India developed dementia at a far lower rate than comparable populations in the U.S. and Western Europe. Most cases of AIDS in India are due to infection with clade C, while most HIV cases in the U.S. and Western Europe are due to clade B.

They thus began searching for genetic variations between two clades, or subtypes, of HIV to explain the differing rates. The investigators compared the sequences of the Tat protein, which helps HIV replicate and leads the attack on patients’ brains, of the two clades. They found that in clade B the Tat protein contained the amino acid cysteine at a specific position whereas in clad C Tat exhibited amino acid serine in the same place.

Next, scientists compared the two viruses in mice to determine whether this key change in the amino acid sequence makes a practical difference in HIV’s neurotoxicity. The researchers injected either clade B or clade C HIV into the brain of a special strain of immunodeficient mice. After six days the mice were tested in a complex water maze that challenged their long-term and short-term memory.

Mice infected with clade B performed significantly worse in the maze than those infected with clade C. Moreover, when the researchers examined the mouse brains, they found more damage to neurons in mice injected with clade B than with clade C. Further, test tube studies showed strain differences in recruiting inflammatory cells to the brain.

Researchers from Albert Einstein College of Medicine of Yeshiva University, the Medical University of South Carolina, the Jawaharlal Nehru Centre for Advanced Scientific Research, and Arizona State University collaborated on the study. The results are published in Journal of Neuroscience.

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