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Updated: Jul 23, 2026

Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
Early steps of polyomavirus entry into cells
1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. jgilbert@hms.harvard.edu
Abstract:
The mechanism by which murine polyomavirus penetrates cells and arrives at the nucleus, the site of viral replication, is not well understood. Simian virus 40 and JC virus, two closely related members of the polyomavirus subfamily, use caveola- and clathrin-mediated uptake pathways for entry, respectively. The data presented here indicate that compounds that block endocytosis of both caveola- and clathrin-derived vesicles have no effect on polyomavirus infectivity. Polyomavirus does not appear to colocalize with either clathrin light chain or caveolin-1 by immunofluorescence microscopy. Additionally, expression of a dominant-negative form of dynamin I has no effect on polyomavirus uptake and infectivity. Therefore, polyomavirus uptake occurs through a class of uncoated vesicles in a clathrin-, caveolin-1-, and dynamin I-independent manner.
Insights
Murine polyomavirus enters cells via a novel pathway, independent of clathrin and caveolin-1. This discovery reveals a new mechanism for viral entry, crucial for understanding polyomavirus infection.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- The cellular entry mechanisms of murine polyomavirus remain largely unknown.
- Related polyomaviruses like Simian virus 40 and JC virus utilize distinct endocytic pathways (caveola- and clathrin-mediated, respectively).
Purpose of the Study:
- To elucidate the cellular uptake mechanism of murine polyomavirus.
- To determine if murine polyomavirus employs clathrin- or caveolin-1-mediated endocytosis for cell entry.
Main Methods:
- Infectivity assays using compounds that inhibit endocytosis.
- Immunofluorescence microscopy to assess colocalization with clathrin and caveolin-1.
- Uptake studies using a dominant-negative dynamin I mutant.
Main Results:
- Inhibitors of caveola- and clathrin-mediated endocytosis did not affect polyomavirus infectivity.
- Murine polyomavirus did not colocalize with clathrin light chain or caveolin-1.
- Dynamin I inhibition did not impact polyomavirus uptake or infectivity.
Conclusions:
- Murine polyomavirus utilizes a clathrin-, caveolin-1-, and dynamin I-independent pathway for cellular entry.
- Viral uptake occurs via a distinct class of uncoated vesicles, differing from related polyomaviruses.
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