Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins

Sakata, Masafumi; Tani, Hideki; Anraku, Masaki; Kataoka, Michiyo; Nagata, Noriyo; Seki, Fumio; Tahara, Maino; Otsuki, Noriyuki; Okamoto, Kiyoko; Takeda, Makoto; Mori, Yoshio

Even among non-immune cell lines RV infection efficiency differs dramatically, although our data using a pseudotype virus system shows that non-immune cells are generally susceptible to RV. These data suggest that the permissibility to RV infection differs considerably among non-immune cell lines. One possible factor modulating the RV infectivity is the host innate immune system. RV is highly sensitive to interferon (IFN) 3, 47, 48 , and the infectivity of individual cell lines with RV is affected by their capacity for IFN production and response to IFN. Vero cells are defective in IFN production 49, 50 , and JEG3 and JAR trophoblast cell lines, which support RV infection most efficiently, are refractory to IFN 51, 52 . Therefore, the activity of innate immunity in individual cells at least partially determines the cell or tissue tropism of RV infection. CRS is a major concern in RV infections. The high infectivity of RV in trophoblast cell lines is an interesting observation that could open a door towards understanding the establishment of RV infection in the fetus after it crosses the placenta. In the fetus, persistent infection of the endothelial cells of the fetal vessels with RV is probably a cause of CRS, because it may induce vascular abnormalities, resulting in dysfunctional or abnormal development of multiple fetal organs or tissue 53 . Perelygina et al. have shown that human fetal endothelial cells are persistently infected with RV 54, 55 . Further studies on the cell and tissue tropism of RV and the molecular mechanisms involved in such tropism are essential if we are to understand the pathophysiology of rubella and CRS. The new RV pseudotype system established in the present study will make a positive contribution to these additional studies. Plasmid constructs. The expression plasmid encoding the precursor protein for the structural proteins (C, E2 and E1) of the RV Hiroshima strain (pcDNA3.1-SP/C 1-300 ) has been described previously 33 . The expression plasmid encoding only E2 and E1 proteins of the RV Hiroshima strain (pcDNA3.1-E2E1) has been described previously 33 . The expression plasmids encoding the envelope proteins of VSV (pC-VSV-G), the Edmonston vaccine strain of MV (pCA7PS-Ed-H and pCXN-Ed-F), and MLV (pFBASALF) have also been described previously 13, 58-60 . pcDNA3.1-SP/C 1-300 is hereafter referred to as pcDNA3.1-CE2E1.