MGH Logo Natural killer (NK) cells are a part of preliminary bodily defenses against an infection. As per a research conducted by a team of scientists at Ragon Institute of MGH, MIT and Harvard, specific strains of HIV related to certain receptor molecules on their NK cells seemingly had different types of basic proteins. This implicated that the virus had presumably ceased its functioning to forgo NK cell reactivity.

An initial analysis showed that some affected individuals had certain versions of gene encryption for NK cell receptors known as killer immunoglobulin-like-receptors (KIR). The latter seemed to offer enhanced control over HIV viral levels. But do they regulate HIV expansion through direct identification of impaired cells or some other subtle system remains a mystery. The researchers designed a study to affirm the hypothesis that mutations in HIV proteins due to some KIRs may allow the virus to let go the NK cell activity. If it holds true then it could probably support the role of NK cells in HIV subjugation.

“This study suggests for the first time that NK cells can impose immune pressure on HIV, something that had previously been described only for T cells and antibodies, adding an additional cell to the repertoire of those with anti-HIV activity. The challenge now will be to translate those findings into new preventive or treatment strategies,” explained Marcus Altfeld, MD, PhD, of the Ragon Institute and Massachusetts General Hospital (MGH), and senior author.

The investigators observed patterns of both HIV proteins and genes encrypting KIR molecules that influence NK cell activity in specimens from 91 infected individuals. They linked variants in viral proteins to the presence of KIR genes with the help of tools that located drug resistance mutations. This was done by spotting changes in the viral genome while the drug is in use. This implies that the virus apparently ceases to function while responding to NK-cell-mediated anti-HIV activity.

The analysts also found that patients whose NK cells were inclusive of an inhibitory receptor called KIR2DL2 looked like carriers of variant forms of HIV that accelerate the communication between the virus and the receptor. This possibly switched off the cell-killing process. These kinds of cells, although prohibited HIV replication in common forms of the disease, a variant form persisted to extend.

The outcomes showed that those who carried KIR2DL2 and HIV seemed to cause mutations that escaped mortality by KIR2DL2-positive NK cells. These mutations seemingly did not take place in persons who did not express the receptor. The scientists believe that since HIV undergoes mutations swiftly, this seems to be one of the avenues to withhold immune system pressure. Considering that HIV does not have infinite capability to alter its sequences, future therapies may involve the combination of varied anti-HIV arms of the immune system to control the virus.

The research is published in the August 4 issue of Nature.