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Published on: July 13, 2019
5-HT2 receptors facilitate JC polyomavirus entry
Benedetta Assetta1, Melissa S Maginnis, Irene Gracia Ahufinger
1Graduate Program in Pathobiology, Brown University, Providence, Rhode Island, USA.
JC polyomavirus (JCPyV) uses the lactoseries tetrasaccharide c (LSTc) for attachment and serotonin 5-HT2 receptors to enter cells. This clarifies JCPyV infection mechanisms, aiding in understanding progressive multifocal leukoencephalopathy (PML) pathogenesis.
Area of Science:
- Virology
- Cell Biology
- Neuroscience
Background:
- Human JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a severe neurological disease.
- JCPyV infection requires lactoseries tetrasaccharide c (LSTc) for attachment and the 5-hydroxytryptamine (5-HT) 2A receptor (5-HT2AR), but the receptor's exact role is unclear.
Purpose of the Study:
- To elucidate the specific roles of serotonin receptors in JCPyV infection.
- To determine which serotonin receptor isoforms facilitate JCPyV entry into host cells.
Main Methods:
- HEK293A cells, which are poorly permissive to JCPyV, were transfected with 14 different serotonin receptor isoforms.
- JCPyV infection, viral attachment, and internalization were analyzed in transfected cells.
- The effect of soluble LSTc on JCPyV infection was assessed.
Main Results:
- Only 5-HT2 receptors (including 5-HT2AR) supported JCPyV infection; other isoforms did not.
- Expression of 5-HT2 receptors significantly enhanced JCPyV internalization but not initial attachment.
- JCPyV infection remained dependent on LSTc, confirming its role as the primary attachment receptor.
Conclusions:
- LSTc is the essential attachment receptor for JCPyV.
- Type 2 serotonin receptors play a critical role in facilitating JCPyV entry into host cells.
- Understanding these entry mechanisms can inform strategies against JCPyV-associated diseases like PML.
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