MxB is an interferon-induced restriction factor of human herpesviruses

Abstract

The type I interferon (IFN) system plays an important role in controlling herpesvirus infections, but it is unclear which IFN-mediated effectors interfere with herpesvirus replication. Here we report that human myxovirus resistance protein B (MxB, also designated Mx2) is a potent human herpesvirus restriction factor in the context of IFN. We demonstrate that ectopic MxB expression restricts a range of herpesviruses from the Alphaherpesvirinae and Gammaherpesvirinae, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), and Kaposi’s sarcoma-associated herpesvirus (KSHV). MxB restriction of HSV-1 and HSV-2 requires GTPase function, in contrast to restriction of lentiviruses. MxB inhibits the delivery of incoming HSV-1 DNA to the nucleus and the appearance of empty capsids, but not the capsid delivery to the cytoplasm or tegument dissociation from the capsid. Our study identifies MxB as a potent pan-herpesvirus restriction factor which blocks the uncoating of viral DNA from the incoming viral capsid.

Overexpression of human MX2 gene suppresses cell proliferation, migration, and invasion via ERK/P38/NF‐κB pathway in glioblastoma cells

“…Previous vast research reported that MXA had broad antiviral activities, while MXB was considered lacking antiviral activity. Recent experiments proved MXB protein encoded by MX2 gene was an interferon‐induced restriction factor of HIV‐1 . However, few studies have been done to explore whether the expression level of MX2 gene was related with tumorigenesis and progression.…”

“…31 protein encoded by MX2 gene was an interferon-induced restriction factor of HIV-1. [19][20][21] However, few studies have been done to explore whether the expression level of MX2 gene was related with tumorigenesis and progression. Our work found that relative messenger RNA (mRNA) levels of MX2 were significantly reduced in both GBM tissues and four glioma cells compared to normal tissues and cells, especially in U251 cells.…”

“…[15][16][17][18] There are 63% identical amino acid sequence both in human MXB and MXA protein, furthermore, the one's three dimensional structure of protein is nearly superimposable with the other. 18 Latest studies found it acted as an interferoninduced restriction factor targeting HIV-1, [19][20][21] which could bind to HIV-1 capsid and inhibit its nuclear import, finally leading to the suppression of its replication at postentry steps. [22][23][24][25][26] This indicated that MXB participated in innate immune responses which were very important for both virus infection and tumor development.…”

Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease

“…To directly visualize HSV-1 entry in macrophages and fibroblasts, we performed electron microscopy of macrophages and fibroblasts, which were infected with HSV-1 (MOI 250) for 30 min. We chose 30 min, as this is the time that HSV-1 requires to enter cells and first incoming capsids to reach the nuclear envelope of fibroblasts or epithelial cells 11,[32][33][34] . Indeed, 30 min after infection we detected first viral capsids at the nuclear envelope of fibroblasts, but no newly produced viral capsids ( Supplementary Fig.…”

Deep learning of virus infections reveals mechanics of lytic cells

“…S1A). We used wild type AdV-C2 and immuno-staining, or the GFP-expressing replication-competent AdV-C2-dE3B-GFP, AdV-C2-dE3B-dADP, AdV-C2-V-GFP, HSV-1-VP16-GFP, HSV-1 C12 viruses (44)(45)(46). For AdV, we acquired images at 72 h post infection (pi), and for HSV-1 at 48 h pi, reflecting the different replication times of the viruses.…”