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IISc develops artificial enzymes to block HIV reactivation

Bengaluru, April 1 (IANS) Indian Institute of Science (IISc) researchers developed artificial enzymes to block reactivation and replication of Human Immuno-deficiency Virus (HIV) in the immune cells, said the premier institute on Thursday.

“Made from vanadium pentoxide nanosheets, the artificial enzymes or nanozymes work by mimicking a natural enzyme that helps reduce oxidative stress levels in the host’s cells to keep the virus in check,” said a study by two researchers at the institute.

Microbiology department’s associate professor Amit Singh and inorganic and physical chemistry department’s professor Govindaswamy Mugesh conducted the study, which was published in “Embo Molecular Medicine” journal.

As there is no process to remove HIV from a patient’s body, anti-HIV drugs only suppress the virus but not eradicate it (HIV) from infected cells.

“The virus hides inside immune cells in a ‘latent’ state and maintains its reservoir. When levels of toxic molecules such as hydrogen peroxide increase in cells, the virus gets reactivated and begins replicating,” said the study.

According to Mugesh, the advantage is nanozymes are stable inside biological systems and do not mediate reactions inside cells. They (nanozymes) can be prepared in a lab.

Earlier, Singh’s team developed a biosensor to measure oxidative stress levels in HIV-infected immune cells in real-time.

“We found that to come out of latency and reactivate, HIV needs very little oxidative stress,” said Singh.

One way to prevent reactivation is to keep the oxidative stress low, which would ‘lock’ the virus in a permanent latent state.

Enzymes such as glutathione peroxidase are essential for the process, as they convert toxic hydrogen peroxide into water and oxygen.

Mugesh’s team also published a study showing that nano-wires made of vanadium pentoxide can mimic the activity of glutathione peroxidase.

Singh’s lab decided to collaborate with the Mugesh team.

The teams prepared ultrathin nanosheets of vanadium pentoxide in the lab and treated HIV-infected cells with them.

The nanosheets were found to reduce hydrogen peroxide as effectively as a natural enzyme and prevent the virus from reactivating.

“We found that nanosheets have a direct effect where the expression of the host genes essential for virus reactivation is reduced,” said the study’s first author Shalini Singh, a research associate at Centre for Infectious Diseases Research (CIDR) here.

When cells from HIV-infected patients undergoing anti-retroviral therapy (ART) were treated with nanozymes, latency was induced faster and reactivation was suppressed when therapy was stopped.

Combining ART with nanozymes also has other advantages.

Some ART drugs can cause oxidative stress as a side-effect, which can damage heart or kidney cells.

“Adding a nanozyme can help reduce side-effects caused by such ART drugs. It can also improve the quality of life of HIV patients undergoing treatment,” added Mugesh.



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