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Published on: January 24, 2016
Interferon-Induced Transmembrane Protein 3 (IFITM3) Restricts PRRSV Replication via Post-Entry Mechanisms
Pratik Katwal1, Shamiq Aftab1, Eric Nelson2
1Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA.
Abstract:
Interferon-induced transmembrane protein 3 (IFITM3) is a member of the family of interferon-stimulated genes (ISGs) that inhibits a diverse array of enveloped viruses which enter host cells by endocytosis. Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus causing significant economic losses to the swine industry. Very little is known regarding how IFITM3 restricts PRRSV. In this study, the role of IFITM3 in PRRSV infection was studied in vitro using MARC-145 cells. IFITM3 over-expression reduced PRRSV replication, while the siRNA-induced knockdown of endogenous IFITM3 increased PRRSV RNA copies and virus titers. The colocalization of the virus with IFITM3 was observed at both 3 and 24 h post infection (hpi). Quantitative analysis of confocal microscopic images showed that an average of 73% of IFITM3-expressing cells were stained positive for PRRSV at 3 hpi, while only an average of 27% of IFITM3-expressing cells were stained positive for PRRSV at 24 hpi. These findings suggest that IFITM3 may restrict PRRSV at the post-entry steps. Future studies are needed to better understand the mechanisms by which this restriction factor inhibits PRRSV.
Insights
Interferon-induced transmembrane protein 3 (IFITM3) restricts porcine reproductive and respiratory syndrome virus (PRRSV) replication in cells. IFITM3 appears to inhibit PRRSV post-entry, offering insights into viral restriction mechanisms.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-stimulated gene known to restrict enveloped viruses.
- Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic damage to the swine industry.
- The mechanism by which IFITM3 restricts PRRSV remains largely unknown.
Purpose of the Study:
- To investigate the role of IFITM3 in restricting PRRSV infection in vitro.
- To elucidate the stage at which IFITM3 exerts its antiviral effect against PRRSV.
Main Methods:
- Utilized MARC-145 cells for in vitro studies.
- Employed IFITM3 overexpression and siRNA-mediated knockdown.
- Performed colocalization studies using confocal microscopy and quantified viral RNA and titers.
Main Results:
- Overexpression of IFITM3 significantly reduced PRRSV replication.
- Knockdown of IFITM3 using siRNA increased PRRSV RNA copies and virus titers.
- Colocalization of PRRSV and IFITM3 was observed, with reduced viral presence in IFITM3-expressing cells over time (73% at 3 hpi vs. 27% at 24 hpi).
Conclusions:
- IFITM3 demonstrates a significant inhibitory effect on PRRSV replication.
- Findings suggest IFITM3 restricts PRRSV at post-entry stages.
- Further research is warranted to fully understand the molecular mechanisms of IFITM3-mediated PRRSV restriction.
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