Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product

Krug, Robert M.; Shaw, Michael; Broni, B.; Shapiro, G.; Haller, Otto

doi:10.1128/jvi.56.1.201-206.1985

Cited by 147 publications

(53 citation statements)

References 22 publications

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“…Mx proteins that are induced by interferons are also known as selective inhibitors of influenza virus growth. Mouse Mx1 protein with GTPase activity is a dynamin‐like protein in cell nuclei and represses, directly or indirectly, viral transcription (Mayer & Horisberger 1984; Krug et al . 1985).…”

Section: Discussionmentioning

confidence: 99%

Host factor Ebp1: Selective inhibitor of influenza virus transcriptase

2007

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Influenza virus RNA polymerase is composed of three virus-coded proteins, and is involved in both transcription and replication of the negative-strand genome RNA. Subunit PB1 plays key roles in both the RNA polymerase assembly and the catalytic function of RNA polymerization. Using yeast two-hybrid screening, a HeLa cell protein with the molecular mass of 45 kDa was identified. After cloning and sequencing, this protein was identified to be Ebp1, ErbB3-binding protein. Epb1 specifically interacts with PB1 both in vitro and in vivo , and Epb1 contact site on PB1 was mapped at its binding site of transcription primers. Ebp1 was found to interfere with in vitro RNA synthesis by influenza virus RNA polymerase (3P complex), but no inhibition was observed for capped RNA endonuclease and RNA-cap binding, the intrinsic activities of RNA polymerase. Since inhibition was not observed against other nucleic acid polymerases tested, we propose that Ebp1 is a selective inhibitor of influenza viral RNA polymerase. Accordingly over-expression of Ebp1 interfered with virus production. The PB1-contact site on Ebp1 overlaps with the interaction site with ErbB3 (epidermal receptor tyrosine kinase), androgen receptor (AR) and retinoblastoma gene product (Rb), which are involved in controlling cell proliferation and differentiation.

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Section: Discussionmentioning

confidence: 99%

Host factor Ebp1: Selective inhibitor of influenza virus transcriptase

2007

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“…What is known is that virns adsorption, penetration, uncoating, and transport of the influenza virus are not affected by Mx protein fimction {77-19). For influenza virus infections, Mxl expression in mouse cells was correlated with a reduction in primary transcription of the viral genes PBl, PB2, and PA (80). The transcription levels of these genes were decreased hy approximately 50-fold (62).…”

Section: Mode Of Action For MX Proteinsmentioning

confidence: 99%

Interferon‐inducible Mx proteins in fish

Leong

Trobridge

Kim

et al. 1998

Immunological Reviews

105

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Mx proteins are members of a family of interferon-inducible genes expressed when cells are treated with double-stranded RNA or virus infection. These proteins are important components of the antiviral response and form the first line of the body's defense against virus infections. The exact mechanism of action for these proteins has not been discovered, but mice missing the Mx genes are extremely sensitive to influenza virus infection. Mammals have between two and three Mx genes whose functions may vary with regard to the inhibition of a specific virus, cellular localization, and activity. The cDNA of three rainbow trout Mx proteins has been cloned and a comparison of their sequences with that of avian and mammalian species reveals striking conservation of domains. They all maintain the tripartite ATP/GTP binding domain and the dynamin family signature in the amino terminal half of the protein. In the carboxyl terminal half of the Mx proteins are the localization signals and the leucine zipper motifs which account for the trimerization of Mx in the cell. Like the rat and human Mx proteins, the different trout Mx proteins exhibit distinctly different immunohistochemical staining patterns in cells transfected with plasmids expressing RBTMx1, RBTMx2, or RBTMx3. To date, the antiviral function of the trout Mx proteins has not been satisfactorily established.

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“…However, such Mxl-negative mice can be rendered resistant to lethal influenza infection by germ line transformation with an Mxl cDNA (4). The precise molecular mechanism for inhibition of influenza viruses is unknown, but it appears that an early step after entry and before accumulation of viral proteins is blocked (13,16).…”

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Activity of rat Mx proteins against a rhabdovirus

Meier

Kunz

Haller

et al. 1990

J Virol

Self Cite

128

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Upon stimulation with alpha/beta interferon, rat cells synthesize three Mx proteins. Sequence analysis of corresponding cDNAs reveals that these three proteins are derived from three distinct genes. One of the rat cDNAs is termed Mxl because it is most closely related to the mouse Mxl cDNA and because it codes for a nuclear protein that, like the mouse Mxl protein, inhibits influenza virus growth. However, this protein differs from mouse Mxl protein, in that it also inhibits vesicular stomatitis virus (VSV), a rhabdovirus. A second rat cDNA is more closely related to the mouse Mx2 cDNA and directs the synthesis of a cytoplasmic protein that inhibits VSV but not influenza virus. The third rat cDNA codes for a cytoplasmic protein that differs from the second one in only eight positions and has no detectable activity against either virus. These results indicate that rat Mx proteins have antiviral specificities not anticipated from the analysis of the murine Mxl protein.

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Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product

Cited by 147 publications

References 22 publications

Host factor Ebp1: Selective inhibitor of influenza virus transcriptase

Host factor Ebp1: Selective inhibitor of influenza virus transcriptase

Interferon‐inducible Mx proteins in fish

Activity of rat Mx proteins against a rhabdovirus

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