The human immunodefiency virus (HIV) while weakening and compromising the body’s immunity, is also believed to trigger HIV-associated dementia (HAD) by infecting the central nervous system. This in turn could lead to complex neurological and behavioural problems as a result of neuro-inflammatory manifestations in the brain due to infection.
In a study conducted by scientists from the Hyderabad-based Centre for Cellular and Molecular Biology (CCMB), the role of a particular protein — HIV-1 TAT protein — was examined. It was found that the extra cellular secretions of this protein modulated the expression of a key gene involved in immune response. This happened through microRNA which plays a vital role in gene regulation.
According to Dr. Sunit Kumar Singh, whose group carried out the study, neurocognitive disorders among HIV-infected individuals have increased from 30 per cent in the 1990s to 50 per cent in 2009.
As the viral infection enters the brain, the TAT protein is one of the earliest to be expressed, he explained. The extra-cellular secretions of the protein from the infected cells affect the non-infected cells in a bystander fashion. This would have an adverse affect and could also lead to cell death.
At CCMB, the scientists have cloned and expressed a recombinant HIV-1 TAT protein and exposed it to human microglial cell lines. Microglial cells are the resident macrophages in the central nervous system. They found that microRNA-32 in the cells exposed to the protein was highly expressed compared with the controls. Through the enhanced activity, microRNA-32 targeted an adaptor protein (TRAF-3). The adapter protein plays an important role in immune signalling pathways.
“We have demonstrated that the adapter protein gets targeted by microRNA-32 after exposure to HIV-1 TAT protein,” Dr. Singh said.
The finding showed how the extra-cellular secretion released by the proteins could modulate expression of genes involved in immune signalling in microglial cells through microRNA-32-mediated pathway.
Overall, this study could help in understanding detrimental neuro-inflammatory manifestations in brain cells caused by HIV-1 TAT protein through micro-RNA-32. However, it would not be possible to target such proteins therapeutically until a delivery mechanism that could overcome the problem of blood-brain barrier was developed.
