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Viral Genetic Underpinnings of HIV-associated Dementia Explored

Science Update

A new study identifies differences between genetic variants of HIV that are associated with HIV-associated dementia (HAD).

Background

HAD, a common symptom affecting the central nervous system and cognitive skills among those infected with HIV, is more common and more severe in patients with a certain genetic variant, called clade B HIV. This particular variant of HIV-1 is more common in North America and Western Europe. Many researchers have found that people infected with the variant of HIV called clade C, common in India, are less likely to have HAD. The mechanisms underlying these genetic and regional differences have been unclear.

Vinayaka R. Prasad, Ph. D., of the Albert Einstein College of Medicine in Bronx, New York, and colleagues exposed genetically engineered mice to clade C HIV and clade B HIV and subjected them to trials involving a maze, in which their working memory was tested over a period of 12 days.

Results of this study

Mice exposed to clade B HIV made significantly more short-term and long-term memory errors and displayed more severe cognitive problems than control mice, and significantly more long-term memory errors than mice exposed to clade C.

The brains of each group of mice had similar levels of HIV-positive cells, but the brains of those exposed to clade B HIV showed more severe neuronal damage than those exposed to clade C HIV. Mice exposed to clade-B HIV also displayed a significantly higher degree of breakdown in the connections between neurons, a hallmark of HAD, compared to clade-C HIV-exposed mice, thus leading to learning and memory problems. The mice exposed to clade B HIV also had more cells called astrocytes, another key feature in HAD, compared to mice exposed to clade C HIV.

Significance

This study was the first to use mouse models to identify the role of HIV genetic variants in the development of HAD.  The study demonstrates that viral genetic differences can affect the severity of HAD, and provides proof of differences between genetic variants in HIV.

What’s next?

The results can be used to help pinpoint specific HIV genes that are directly involved in the chain of events that can lead to HAD. The data provides more detail that will help researchers target specific genes responsible for the development of HAD and thereby find better treatments for HAD.

Reference

Rao VR, Sas AR, Eugenin EA, Siddappa NB, Bimonte-Nelson H, Berman JW, Ranga U, Tyor WR, Prasad VR. HIV-1 clade-specific differences in the induction of neuropathogenesis . The Journal of Neuroscience. 2008 Oct 1; 28(40): 10010-10016.