Remember ME - You Me and Dementia

Tuesday, January 22, 2008

Why less Indians suffer AIDS dementia

The mystery - why only 4% of Indian HIV patients suffered from AIDS-induced dementia as against 45% of those in the West (US and Europe) - may have finally been cracked.

A six-member team from the National Brain Research Centre (NBRC) has found that Tat - the neuro-toxic protein in the AIDS virus that causes dementia -undergoes a natural mutation, especially in the HIV1-C type (the virus type specific to India), which reduces its neuro-toxicity by almost 100%.

There are 10 strains of HIV that infect people worldwide. The Indian strain HIV1-C is the only one that undergoes this mutation, making Tat ineffective in HIV infected Indians.

"This is why India records such low incidence of AIDS-induced dementia compared to the West, where the virus does not undergo this mutation," Pankaj Seth, scientist in-charge of the NeuroAIDS lab at NBRC, told TOI.

For the past two years, Dr Seth's laboratory has been studying the role of Tat protein derived from HIV strains B and C to understand the neuro effects of HIV infection in the brain.

"We have now, for the first time, demonstrated this natural mutation in Tat in the Indian strain of HIV, which reduced the neuro-toxicity of this HIV protein. The project was funded by the department of biotechnology," Seth said.

The team has announced its findings in the January edition of 'Annals of Neurology', a prestigious international journal of clinical neurology.

HIV-induced dementia or AIDS dementia complex (ADC) develops in the advanced stages of HIV infection.

It is a common source of morbidity and causes memory, learning, behavioural and motor disabilities. It also interferes with a patient's ability to adhere to a regular course of ART medication.

Seth, who is associate professor of molecular and cellular neuroscience at NBRC, said, "We carried out the study with the help of a novel human brain derived neural stem cell culture system that was developed at NBRC. It was earlier known that Tat destroys the neurons - an irreversible mechanism. What we did was to use cells isolated from human fetal brain material to understand how TAT affected the neurons.

"Our findings suggest that HIV Tat protein from subtype C infected patients is less damaging to neurons as compared to Tat B."

The team then reversed the mutation in the virus and found that Tat's tremendous neurotoxicity returned. "This confirms that the natural mutation in the Indian HIV strain C makes it less toxic to the brain and therefore does not cause dementia," Seth added.

In India, HIV1-C accounts for over 95% of HIV infections.



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