Viral infections, such as those caused by varicella-zoster virus (VZV), are often difficult to come across for in vivo study. However, a North American based research group consisting of Katherine S. Lee and colleagues recently established a method to study such viral pathogens using induced pluripotent stem (iPS) cells. Specifically, iPS cells were differentiated into sensory neuron cells in order to support the VZV life-cycle, so it could be studied while alive.
Varicella-zoster virus causes the family of infections that includes chickenpox and its elder, more painful sibling, shingles. This virus as well as the herpes simplex virus (HSV) are known to infect and dwell within human sensory neurons, which is why sensory neuron cells were of interest in this study. Many models used to study these viruses in vivo such as those using small animals, non-human primates, human tissue engraftments, and human primary neuron isolations fall short with such caveats as high cost and limited sample availability. However, growing sensory neuron cells from iPS cells in which to host the virus subverts both.
The process of differentiating iPS cells into sensory neuron cells takes about one month. Starting from human embryonic fibroblast cells, iPS cells were induced. Following, small molecule inhibitors were introduced converting the iPS cells into neural progenitor cells (NPCs), neural stem cells. Lastly, the NPCs were exposed to growth factors such as NGF, which finalized them as sensory neuron cells.
ßIII-tubulin and Brn3a were two secreted proteins looked for when determining the population change into sensory neurons. 15% of the original cell population differentiated into sensory neuron cells. After infecting with VZV virus, it was determined that only differentiated sensory neuron cells, not original iPS cells, could support the virus.
iPS cell derived sensory neurons were able to successfully permit and support VZ viral infection. This method of rapid and reproducible growth of viral host cells will prove useful in studying viruses and testing anti-viral treatments. Grow your enemy, understand your enemy, beat your enemy.
Katherine S. Lee, Wenbo Zhou, Jonah J. Scott-McKean, Kaitlin L. Emmerling, Guang-yun Cai, David L. Krah, Alberto C. Costa, Curt R. Freed, Myron J. Levin. 2012. Human Sensory Neurons Derived from Induced Pluripotent Stem Cells Support Varicella-Zoster Virus Infection. PLoS ONE.