Pseudotyped SARS-CoV-2 particles enter human neural stem cells via endocytosis

Laboratory experiments found that pseudotyped viral particles carrying SARS-CoV-2 spike proteins representing the wild-type virus and Omicron variants efficiently transduced human neural stem cells. The particles were used to examine entry mechanisms, not to reproduce the complete course of infection in people.

Omicron spike variants showed a preferential use of an endocytosis-mediated entry pathway in the neural stem cells. The study assessed this behavior in cultured human cells and did not establish how frequently infection occurs in a developing human nervous system.

Two endocytosis inhibitors, filipin and OcTMAB, significantly reduced viral entry across all tested spike variants. The reported abstract does not provide the size of these reductions or establish whether additional entry routes also contributed.

The investigators also found that relatively low glycosylation levels on the neural stem cells facilitated viral entry. Enzymatic removal of glycosylation increased the cells’ susceptibility to the tested pseudotyped particles, supporting an influence of cell-surface glycosylation on entry.

The researchers had hypothesized that neural stem cells derived from human ectoderm would be susceptible to SARS-CoV-2 after previous work showed greater susceptibility among ectodermal cells than among endodermal and mesodermal cells. Their experiments confirmed susceptibility under the laboratory conditions used.

These cell-culture findings do not demonstrate infection, congenital abnormalities or neurodevelopmental deficits in children exposed during pregnancy. They also do not show that the entry mechanism identified in neural stem cells operates identically throughout the developing nervous system or over the course of a natural infection.

Despite those limitations, the authors said that ectodermal infection raises concern about potential teratogenic effects on the nervous system. Such effects could be latent or subclinical and therefore not immediately evident at birth, but the reported experiments did not measure those outcomes.

The authors called for clinical studies and long-term surveillance of infants and children exposed in utero to investigate possible neurodevelopmental deficits. Whether such deficits occur, and how frequently, remains unresolved by the reported cell experiment.

Subject of Research: Cell-culture study of SARS-CoV-2 spike-variant entry into human neural stem cells

Article Title: Susceptibility of human neural stem cells to SARS-CoV-2: Entry mechanisms and glycocalyx influence

Article References: Song, A., Zuvia, C., & Talbot, P. (2026). Susceptibility of human neural stem cells to SARS-CoV-2: Entry mechanisms and glycocalyx influence. PLOS One, 21(10), e0360734. https://doi.org/10.1371/journal.pone.0360734

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0360734

Keywords: SARS-CoV-2, neural stem cells, viral entry, endocytosis, Omicron, glycosylation, ectoderm, pseudotyped particles, neurodevelopment, Susceptibility, human, neural