Promoted Cell Death of Cells Expressing Human MxA by Influenza Virus Infection

Abstract

Interferon‐inducible MxA protein plays a crucial role in cellular protection from RNA virus infection, although the protection mechanism is not completely clarified. Here, we examined effects of MxA on either uninfected or influenza virus A/PR/8/34‐infected cells. Viral protein synthesis was reduced in cells expressing MxA. Under serum‐starved conditions, not only viral but also cellular protein synthesis was reduced by expression of MxA. Of interest is that MxA promoted cell death induced by apoptotic stimuli as well as influenza virus infection. These results lead to a possibility that MxA suppresses multiplication of influenza virus by affecting cellular functions including the apoptotic pathway.

Induction of MxA Gene Expression by Influenza A Virus Requires Type I or Type III Interferon Signaling

“…Negative effects on the normal homoeostasis of the cell could be provoked by Mx accumulation. Accordingly, MxA overexpression has been shown to increase the sensitivity of cells to apoptotic stimuli (41,50). Thus, it has been suggested that the upregulation of MxA is one factor that promotes the development of Fanconi anemia, a disorder that predisposes patients for skeletal malformation, progression to bone marrow failure, and acute leukemia (41).…”

Structure of Myxovirus Resistance Protein A Reveals Intra- and Intermolecular Domain Interactions Required for the Antiviral Function

“…A direct role of Mx proteins was demonstrated by the fact that the Mx antiviral activity can be neutralized in living cells by microinjection of specific antibodies (Arnheiter and Haller, 1988). Besides its antiviral function, MxA expression has also been linked to increased sensitivity of cells to apoptotic stimuli (Mibayashi et al, 2002) and to inhibition of tumor cell motility and invasiveness (Mushinski et al, 2009). Moreover, the mouse Mx1 protein has been characterized as one of the few minor histocompatibility antigens (Speiser et al, 1990).…”

Single nucleotide polymorphisms and functional analysis of MxA promoter region in multiple sclerosis

“…In addition, the existence of single nucleotide polymorphisms (SNPs) in or near the ISRE on the MxA promoter region was found [2], and the SNPs were thought to correlate with the anti-viral activity of MxA induced by IFN-β [3]. Furthermore, a recent study indicated that MxA may affect specific cellular functions, including the signal transduction of apoptotic pathway [4]. In this study, we investigated the SNPs on the MxA promoter region in patients with MS in order to determine the role of MxA as a possible genetic factor in the development of MS.…”