Study Models the Effect of Herpes Infection on Fetal Brain Development

Three cell-based models shed light on how herpes simplex virus type 1 (HSV-1) infection may contribute to various neurodevelopmental disabilities and long-term neurological problems into adulthood, according to a study published in PLOS Pathogens. HSV-1 can spread to the fetal brain during pregnancy and cause lifelong neurological problems, such as cognitive dysfunction, learning disabilities, and dementia.

Progress in understanding the role of HSV-1 in human fetal brain development has been hampered by restricted access to fetal human brain tissue. Additionally, existing animal models are limited in their applicability to humans. To address the knowledge gap, the investigators generated 3 cell-based neurodevelopmental disorder models, including a 2D layer of cells and a 3D brain-like structure. These models are based on human-induced pluripotent stem cells (hiPSCs), which are immature, embryonic stem cell-like cells. These hiPSCs are generated by genetically reprogramming specialized adult cells.

According to the investigators, HSV-1 infection in neural stem cells derived from hiPSCs resulted in activation of the caspase-3 apoptotic pathway, which initiates programmed cell death. HSV-1 infection also impaired the production of new neurons and hindered the ability of hiPSC-derived neural stem cells to convert into mature neurons through a process called neuronal differentiation.

The study also found that the HSV-1-infected brain organoids mimicked the pathological features of neurodevelopmental disorders in the human fetal brain, including impaired neuronal differentiation and abnormalities in brain structure. In addition, the 3D model showed that HSV-1 infection promotes the abnormal proliferation and activation of non-neuronal cells called microglia, accompanied by the activation of inflammatory molecules, such as TNF-alpha, IL-6, IL-10, and IL-4.

According to the authors, the findings open new therapeutic avenues for targeting viral reservoirs relevant to neurodevelopmental disorders. They added that the study provides novel evidence that HSV-1 infection impaired human brain development and contributes to the neurodevelopmental disorder pathogen hypothesis.

REFERENCE

How herpes infection may impair human fetal brain development [news release]. EurekAlert; October 22, 2020. Accessed May 7, 2021. https://www.eurekalert.org/pub_releases/2020-10/p-hhi101520.php