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Class A Scavenger Receptors Are Used by Frog Virus 3 During Its Cellular Entry.
Vo NTK, Guerreiro M, Yaparla A, Grayfer L, DeWitte-Orr SJ.
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Frog virus 3 (FV3) is the type species of the genus Ranavirus (family Iridoviridae). FV3 and FV3-like viruses are globally distributed infectious agents with the capacity to replicate in three vertebrate classes (teleosts, amphibians, and reptiles). At the cellular level, FV3 and FV3-like viruses can infect cells from virtually all vertebrate classes. To date, the cellular receptors that are involved in the FV3 entry process are unknown. Class A scavenger receptors (SR-As) are a family of evolutionarily conserved cell-surface receptors that bind a wide range of chemically distinct polyanionic ligands and can function as cellular receptors for other DNA viruses, including vaccinia virus and herpes simplex virus. The present study aimed to determine whether SR-As are involved in FV3 cellular entry. By using well-defined SR-A competitive and non-competitive ligand-blocking assays and absolute qPCR, we demonstrated that the SR-A competitive ligands drastically reduced the quantities of cell-associated viral loads in frog cells. Moreover, inducing the expression of a human SR-AI in an SR-A null cell line significantly increased FV3⁻cell association. Together, our results indicate that SR-As are utilized by FV3 during the cellular entry process.
Discovery grant Natural Sciences and Engineering Research Council of Canada, Early Researcher Award Ontario Ministry of Research, Innovation and Science, IOS:1749427 National Science Foundation CAREER Award
Figure 3. Effect of induced human SR-AI (hSR-AI) expression on the cell-associated FV3 loads in
SR-A-null A549 cells. hSR-AI expression was induced with 200 ng/mL doxycycline (DOX). Control
SR-A-null and DOX-treated hSR-AI-expressing cells were infected with FV3 at an MOI of 0.5 for 1 h.
Total DNA was subsequently harvested and subjected to absolute qPCR analyses for FV3 DNA loads.
Data are presented as means SEM (n = 3). Statistical analysis using a Student’s t-test withWelch’s
correction was performed. ***p < 0.001.
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