Persistent echovirus infection of mouse cells expressing the viral receptor VLA-2.
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.
Zhang
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Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 West 168th Street, New York, New York, 10032, USA.
Racaniello
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VR
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D015536:Down-Regulation; D004457:Echovirus Infections / Q000821:virology; D029822:Enterovirus B, Human / Q000254:growth & development / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D039421:Integrin alpha2; D016023:Integrins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D014176:Protein Biosynthesis; D038981:Receptors, Collagen; D013997:Time Factors
D015703:Antigens, CD; D039421:Integrin alpha2; D016023:Integrins; D038981:Receptors, Collagen