4.6 Article

The MAPK/ERK Pathway and the Role of DUSP1 in JCPyV Infection of Primary Astrocytes

期刊

VIRUSES-BASEL
卷 13, 期 9, 页码 -

出版社

MDPI
DOI: 10.3390/v13091834

关键词

JC polyomavirus; progressive multifocal leukoencephalopathy (PML); astrocytes; RNA sequencing; bioinformatics

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资金

  1. National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R15AI144686]
  2. Maine IDeA Network of Biomedical Research Excellence (INBRE) through the National Institute of General Medical Sciences [P20GM103423]
  3. University of Maine: a Biomedical Sciences Accelerator Fund Faculty Award from the College of Natural Sciences, Forestry, and Agriculture
  4. Frederick H. Radke Undergraduate Research Fellowships from the Department of Molecular and Biomedical Sciences
  5. Center for Undergraduate Research Institute of Medicine Fellowship
  6. University of Maine Graduate Student Government

向作者/读者索取更多资源

JC polyomavirus (JCPyV) requires the MAPK/ERK pathway and DUSPs, particularly DUSP1, for successful infection in primary human astrocytes (NHAs). Additionally, immune activation unique to NHAs was observed. These findings provide important insights into the mechanisms of JCPyV infection.
JC polyomavirus (JCPyV) is a neuroinvasive pathogen causing a fatal, demyelinating disease of the central nervous system (CNS) known as progressive multifocal leukoencephalopathy (PML). Within the CNS, JCPyV predominately targets two cell types: oligodendrocytes and astrocytes. The underlying mechanisms of astrocytic infection are poorly understood, yet recent findings suggest critical differences in JCPyV infection of primary astrocytes compared to a widely studied immortalized cell model. RNA sequencing was performed in primary normal human astrocytes (NHAs) to analyze the transcriptomic profile that emerges during JCPyV infection. Through a comparative analysis, it was validated that JCPyV requires the mitogen-activated protein kinase, extracellular signal-regulated kinase (MAPK/ERK) pathway, and additionally requires the expression of dual-specificity phosphatases (DUSPs). Specifically, the expression of DUSP1 is needed to establish a successful infection in NHAs, yet this was not observed in an immortalized cell model of JCPyV infection. Additional analyses demonstrated immune activation uniquely observed in NHAs. These results support the hypothesis that DUSPs within the MAPK/ERK pathway impact viral infection and influence potential downstream targets and cellular pathways. Collectively, this research implicates DUSP1 in JCPyV infection of primary human astrocytes, and most importantly, further resolves the signaling events that lead to successful JCPyV infection in the CNS.

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