Induction of manganese-superoxide dismutase in MRC-5 cells persistently infected with an alphavirus, sindbis.
Sindbis virus (SV), a single-stranded positive-sense RNA virus, multiplies in a variety of cells and causes various outcomes of infection. As we described acute infection of SV induces stress response of small heat shock protein HSP27 and activation of mitogen-activated protein kinase (MAP) signaling pathway (Nakatsue, T., et al., Biochem. Biophys. Res. Commun. 253, 59-64, 1998). In contrast to lytic infection in Vero cells, MRC-5 cells, a human fetus lung cell line, resulted in persistent infection by SV. Here we investigated a cellular factor involved in persistent infection of MRC-5 cells infected with SV. Partial sequence analysis of a 25 kilodalton (kDa) protein, accumulated in large amounts in the cells, showed that manganese-superoxide dismutase (Mn-SOD) was induced during the infections. When Mn-SOD was overexpressed in Vero cells, 20% of the cells survived more than one month, in contrast with the death of 99% of the vehicle-transfected Vero cells at 48 h after infection with SV. These data strongly suggest that a cellular factor which regulates the oxidative pathway modulates the outcome of SV infection.
Yoshinaka
Y
Y
Medical Research Division, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-5810, Japan. yoshi.gene@cmn.tmd.ac.jp
Takahashi
Y
Y
Nakamura
S
S
Katoh
I
I
Takio
K
K
Ikawa
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004790:Enzyme Induction; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000196:embryology; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D012845:Sindbis Virus / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014709:Vero Cells
D000975:Antioxidants; D016166:Free Radical Scavengers; D013482:Superoxide Dismutase