N-Myc Interactor Inhibits Prototype Foamy Virus by Sequestering Viral Tas Protein in the Cytoplasm

Abstract

Foamy viruses (FVs) are complex retroviruses that establish lifelong persistent infection without evident pathology. However, the roles of cellular factors in FV latency are poorly understood. This study revealed that N-Myc interactor (Nmi) could inhibit the replication of prototype foamy virus (PFV). Overexpression of Nmi reduced PFV replication, whereas its depletion by small interfering RNA increased PFV replication. The Nmi-mediated impairment of PFV replication resulted from the diminished transactivation by PFV Tas of the viral long terminal repeat (LTR) and an internal promoter (IP). Nmi was determined to interact with Tas and abrogate its function by sequestration in the cytoplasm. In addition, human and bovine Nmi proteins were found to inhibit the replication of bovine foamy virus (BFV) and PFV. Together, these results indicate that Nmi inhibits both human and bovine FVs by interfering with the transactivation function of Tas and may have a role in the host defense against FV infection. IMPORTANCEFrom this study, we report that the N-Myc interactor (Nmi), an interferon-induced protein, can interact with the regulatory protein Tas of the prototype foamy virus and sequester it in the cytoplasm. The results of this study suggest that Nmi plays an important role in maintaining foamy virus latency and may reveal a new pathway in the interferon-mediated antiviral barrier against viruses. These findings are important for understanding virus-host relationships not only with FVs but potentially for other retroviruses as well.

Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo

“…Moreover, unlike hBST2, bBST2A1 displays no inhibitory effect on cell-to-cell transmission of PFV and BFV [90]. Other antiviral proteins include promyelocytic leukemia protein (PML), IFN-induced 35-kDa protein (IFP35), N-Myc interactor (Nmi), and p53-induced RING-H2 protein (Pirh2), which have been recently shown to inhibit FV replication through interacting with Tas [27,[91][92][93]. PML directly interacts with PFV Tas and it interferes with its ability to bind the TREs in the PFV LTR and IP [91].…”

Origin, evolution and innate immune control of simian foamy viruses in humans

“…FV Bet protein has been shown to partially prevent APOBEC action [40][41][42][43]. N-Myc interactor (NMI) as well as a member of the interferon-induced protein (IFP) family, IFP35, can inhibit the replication of the prototype and the bovine FV respectively, by direct interaction with the viral transactivator Tas [46,47]. Tetherin is known to block many different types of enveloped viruses by tethering the budding virus at the cell membrane and is also efficient to prevent FV release [48,49].…”

N‐myc and STAT interactor correlates with severity and prognosis in acute‐on‐chronic liver failure of hepatitis B virus

“…NMI is elevated rapidly in acetaminophen‐induced liver injury . NMI is also involved in antiviral response against viral infections . Recently, it is demonstrated that NMI correlates with the severity of inflammation in sepsis patients .…”

“…6 NMI is also involved in antiviral response against viral infections. 7 Recently, it is demonstrated that NMI correlates with the severity of inflammation in sepsis patients. 6 The severity of ACLF is also correlated with inflammation, which is contributing to prognosis of ACLF.…”