Effects of mouse hepatitis virus infection on host cell metabolism.
A time dependent decrease in cell surface expression of major histocompatibility complex (MHC) class 1 proteins was found during JHMV infection of the mouse macrophage J774.1 cells line by radioimmunoassay. MHC class I, actin and CSF-1 receptor mRNA levels were also found to decrease during infection. Surprisingly, not all host cell mRNA were similarly affected, suggesting that the apparent MHV-induced translational shut off of host cell protein synthesis during infection was specific for only some host cell mRNAs. Interestingly, two mRNAs found to be refractory to JHMV infection encode monokines, suggesting a role in pathogenesis. To understand the mechanism(s) of this preferential mRNA stability and the apparent shut off of host cell mRNA, translation lysates were prepared from infected and uninfected cells. Translation of host mRNAs in these extracts showed no apparent loss of translational ability in the infected cells vs. the uninfected cells; however, viral mRNAs were preferentially translated in the lysates from the infected cells. Chimeric mRNAs containing the MHV leader upstream of a globin reporter gene showed that preferential translation was a property of the MHV leader RNA. Deletional analysis showed that the sequences responsible for this cis translational augmentation are in a 12 nucleotide (nt) tract at the 3' end of the leader. The previously reported interaction of the nucleocapsid protein with these nts suggest that it may play a role in translational augmentation of MHV mRNAs.
Tahara
S
S
Department of Microbiology, University of Southern California School of Medicine, Los Angeles.
Bergmann
C
C
Nelson
G
G
Anthony
R
R
Dietlin
T
T
Kyuwa
S
S
Stohlman
S
S
D000818:Animals; D005260:Female; D015967:Gene Expression Regulation, Viral; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D006517:Murine hepatitis virus / Q000502:physiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger