Indian twist to HIV brain disorders
doi:10.1038/nindia.2008.191 Published online 28 April 2008
Neurologists have long been intrigued at the remarkably low incidence of HIV-1 associated dementia among Indian AIDS patients. A group of researchers from the National Brain Research Centre (NBRC) in Manesar, Haryana seems to have found why.
The team has worked out how the molecular rearrangements of amino acids in the HIV-1 transactivating protein Tat affects its ability to damage neurons. The team demonstrated that natural mutation at a particular location in the Tat protein of the subtype prevalent in India HIV-1C, perhaps accounts for the significantly reduced neurotoxicity of Tat.
Tat is the transactivating protein that HIV produces to affect genes of the infected cells, as well as non-infected neighbouring cells. Tat also mounts an inflammatory response in the brain cells, ultimately causing irreversible damage to neurons.
The team looked into various parameters of neuronal damage including oxidative stress and differences in the release of a chemo-attractive protein that is implicated in the trafficking of monocytes that transport HIV particles into the brain.
"Our data show differences between the two Tat proteins in their ability to induce toxicity in human neurons and hints at potential differences in how humans can be infected by different HIV subtypes," says Pankaj Seth, the principal investigator of the study.
"The significance of this research finding is that it explains potential molecular basis for why the subtype C may cause milder neuropathogenesis (course of neuronal pathology)," Seth adds.
- Mishra, M. et al. Clade-Specific Differences in Neurotoxicity of Human Immunodeficiency Virus-1 B and C Tat of Human Neurons: Significance of Dicysteine C30C31 Motif. Ann. Neurol. 63, 367-375 (2008)