A mouse virus, Virus A, causes lethal infection in mice through infection and de

Question

A mouse virus, Virus A, causes lethal infection in mice through infection and destruction of cells in the Central Nervous System. The virus infects cells of the meninges, brain parenchyma, choroid plexus, and ependyma. An experiment was conducted in which transgenic mice were created with the gene for perforin deleted. These transgenic mice (Perf -/-) and nomal mice (Perf +/+) were treated with Virus A and the results on survival of the mice are presented below. Explain what aspect of the immune response is being affected by the perforin gene deletion. Explain the paradox of why deletion of a gene involved in the immune response protect these mice from lethal disease.

Explanation / Answer

When mouse virus, Virus A infects the mouse, it destroys the cells of CNS but in transgenic mouse where performing gene was deleted, the mouse CNS is not destroyed. It was seen that removal of the perforin gene protected the mice from lethal diseases. Perforin is a pore forming protein which is released by cytotoxic T cells and it forms transmembrane channels by polymerising with cell plasma membrane of target. Hence, in transgenic mice where the gene for perforin was deleted was not able to produce perforin protein and hence was not able to generate microbe specific cytotoxic T cells. Generally, this led to susceptibility of certain viral and intracellular bacterial infections. It is seen that perforin helps in immune response and regulation.

In this case the paradox is that perforin deficient mice were protected from lethal effects. It was seen that when perforin deficient mice was infected by virus, it contained greater number of anti-viral T-Cells as compared to mice that produced perforin. It was seen that the virus infection specific CD8 T cells were present more in perforin deficient mice. In perforin present mice, due to persistent infections, it continuously led to depletion of the antigen specific CD8 T cells and this exhaustion of cells occurred less in perforin deficient mice. Hence, it was seen that due to accumulation of anti-viral molecules in perforin deficient molecule the mice was protected from the lethal damage caused by Virus A upon infection.

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