Related Experiment Video
Updated: Sep 8, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Persistent echovirus infection of mouse cells expressing the viral receptor VLA-2
1Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 West 168th Street, New York, New York, 10032, USA.
Abstract:
Mouse cells are not susceptible to infection with echovirus 1 (EV-1) because they lack the viral receptor, human VLA-2. Two mouse fibroblast cell lines, L cells and 3T3 cells, were made susceptible to EV-1 infection after transformation with cDNAs of human VLA-2. After EV-1 infection, L cell transformants of human VLA-2 (alpha2beta1 L cells) develop cytopathic effect (CPE) as expected, while 3T3 cell transformants of human VLA-2 (alpha2beta1 3T3 cells) or the alpha2 subunit of human VLA-2 (alpha2 3T3 cells) become persistently infected. The distinct outcome is not a result of differential virus growth on these transformants because one-step growth curve analysis reveals little difference in EV-1 replication in both cell lines. In addition, 3T3 cell transformants expressing the poliovirus receptor (Pvr 3T3 cells) are lysed during poliovirus infection, suggesting that 3T3 cells are not intrinsically resistant to CPE caused by enterovirus infection. The results of limit dilution assays indicate that all EV-1-infected alpha2 3T3 cells produce infectious virus. All EV-1-infected alpha2 3T3 cells remain viable after EV-1 infection, and the kinetics of cell growth were not altered. FACS analysis reveals that receptor down-regulation is not involved in the establishment of persistent infection. Furthermore, inhibition of host protein synthesis was not observed in EV-1-infected alpha2 3T3 or alpha2beta1 L cells. Since alpha2beta1 L cells are lysed by EV-1 infection, these findings suggest that virus-induced translation inhibition is not a determinant of cell killing.
Insights
Mouse cells lack the echovirus 1 (EV-1) receptor, human VLA-2. Introducing this receptor made cells susceptible to EV-1, leading to either cell death or persistent infection, depending on the cell type.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Mouse cells lack the necessary human VLA-2 receptor for echovirus 1 (EV-1) infection.
- Understanding viral entry mechanisms is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the role of human VLA-2 in EV-1 infection susceptibility and outcome in mouse cells.
- To determine the factors influencing persistent infection versus cytopathic effect (CPE).
Main Methods:
- Transfection of mouse L and 3T3 cells with human VLA-2 cDNA.
- Infection of engineered cells with EV-1.
- Analysis of viral replication, cell viability, and host protein synthesis.
Main Results:
- Transformed cells expressing human VLA-2 became susceptible to EV-1.
- L cells exhibited cytopathic effect (cell death), while 3T3 cells developed persistent infections.
- Viral replication and host protein synthesis inhibition did not differ significantly between cell types, suggesting other mechanisms determine infection outcome.
Conclusions:
- The cell type influences the outcome of EV-1 infection, even when the viral receptor is present.
- Mechanisms beyond viral replication and host protein synthesis inhibition determine EV-1-induced cell killing or persistent infection.
