New research models suggest that the herpes simplex virus type 1 (HSV-1) infection can spread to the fetal brain during pregnancy, potentially contributing to various neurodevelopmental disabilities and long-term neurological problems into adulthood.

According to the study, published in PLOS Pathogens, HSV-1 can cause lifelong neurological problems including cognitive dysfunction, learning disabilities, and dementia. Despite these concerns, research into the role of HSV-1 in human fetal brain development has been limited by restricted access to fetal brain tissue and limitations in existing animal models.

To address this knowledge gap, investigators created 3 different cell-based neurodevelopmental disorder models, including a 2-dimensional layer of cells and a 3-dimensional brain-like structure. These models were based on human induced pluripotent stem cells—immature, embryonic stem cell-like cells that are generated by genetically reprogramming specialized adult cells.

HSV-1 infection in the models’ neural stem cells resulted in the activation of the caspase-3 apoptotic pathway, which initiates programmed cell death. The infection also impaired the production of new neurons and hindered the ability of the cells to convert into mature neurons through neuronal differentiation.

Furthermore, the study authors found that the HSV-1-infected brain organoids mimicked the pathological features of neurodevelopmental disorders in the fetal brain, including impaired neuronal differentiation and abnormalities in brain structure. In the 3D model, the investigators noted that HSV-1 infection promoted the abnormal proliferation and activation of non-neuronal cells, in addition to the activation of inflammatory molecules.

According to the authors, these findings open new therapeutic avenues for targeting viral reservoirs relevant to neurodevelopmental disorders.

“This study provides novel evidence that HSV-1 infection impaired human brain development and contributed to the neurodevelopmental disorder pathogen hypothesis,” the authors concluded.

REFERENCE
Quao H, Guo M, Shang J, Zhao W, et al. (2020) Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes. PLoS Pathog 16(10): e1008899. https://doi.org/10.1371/journal.ppat.1008899.