Autor(es): Kreit Marguerite, Vertommen Didier, Gillet Laurent, Michiels Thomas

Resumo: Apolipoprotein L9b (Apol9b) is an interferon-stimulated gene (ISG) that has antiviral activity - is weakly expressed in primary mouse neurons as compared to other cell types. Here, we show that both Apol9 isoforms (Apol9b - Apol9a) inhibit replication of Theiler's murine encephalomyelitis virus (TMEV) but not replication of vesicular stomatitis virus (VSV), Murid herpesvirus-4 (MuHV-4), or infection by a lentiviral vector. Apol9 genes are strongly expressed in mouse liver -, to a lesser extent, in pancreas, adipose tissue - intestine. Their expression is increased by type I interferon - viral infection. In contrast to genuine apolipoproteins that are involved in lipid transport, ApoL9 has an intracytoplasmic localization - does not seem to be secreted. The cytoplasmic localization of ApoL9 is in line with the observation that ApoL9 inhibits the replication step of TMEV infection. In contrast to human ApoL6, ApoL9 did not sensitize cells to apoptosis, in spite of the presence of a conserved putative BH3 domain, required for antiviral activity. ApoL9a - b isoforms interact with cellular prohibitin 1 (Phb1) - prohibitin 2 (Phb2) - this interaction might contribute to ApoL9 antiviral activity. Knocking down Phb2 slightly increased TMEV replication, irrespective of ApoL9 overexpression. The antiviral activity of prohibitins against TMEV contrasts with the pro-viral activity of prohibitins observed for VSV - reported previously for Dengue 2 (DENV-2), Chikungunya (CHIKV) - influenza H5N1 viruses. ApoL9 is thus an example of ISG displaying a narrow antiviral range, which likely acts in complex with prohibitins to restrict TMEV replication.

Imprenta: PloS One, v. 10, n. 7, p. e0133190, 2015

Identificador do objeto digital: 10.1371/journal.pone.0133190

Descritores: Chikungunya virus - Cell ; Chikungunya Virus - Virus ; Chikungunya virus - Dengue

Data de publicação: 2015

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