The MX dynamin GTPases inhibit diverse viruses at early post-entry phases. While MXA acts antiviral against influenza viruses, the anti HIV-1 activity of MXB was discovered recently. Here, we have studied the antiviral effect of MX proteins on murine cytomegalovirus (MCMV). Our data demonstrate that human MXB but not other human or murine MX proteins inhibit MCMV propagation. Evidently, the viral protein expression was delayed and the viral DNA amount in nucleus was diminished in MXB expressing cells indicating an obstruction of nuclear entry. Of note, MCMV did not deplete MX proteins. Considering the role of capsid on HIV-1 sensitivity to MXB, MXB binding to tested MCMV capsids was not detected. Moreover, MCMV restriction occurred only when MXB contained both the nuclear localization signal and a functional GTPase domain. Hence, we propose a new mode of inhibition of MCMV by MXB that is conspicuously different from that of HIV-1.

Foamy viruses (FV) are retroviruses that are widely distributed in primate and non-primate animal species. We tested here FV with capsids of simian and non-simian origin for sensitivity to interferon-β (IFN-β). Our data show significant inhibition of FV by IFN-β early in infection of human HOS and THP-1 but not of HEK293T cells. The post-entry restriction of FV was not mediated by the interferon-induced MxB protein that was recently identified as a capsid-interacting restriction factor targeting Human immunodeficiency virus (HIV) before integration. Neither the ectopic expression of MxA or MxB in HEK293T cells nor the lack of MxB expression in CRISPR/CAS MxB THP-1 knockout cells impacted the infection of the tested FV. IFN-β treated THP-1 and THP-1 KO MxB cells showed the same extend of restriction to FV. Together, the data demonstrate that IFN-β inhibits FV early in infection and that MxB is not a restriction factor of FV.

Human myxovirus resistance protein B (hMXB) is a restriction factor of HIV-1 that also inhibits a variety of retroviruses. However, hMXB is not antiviral against equine infectious anemia virus (EIAV). We show here that equine MX2 (eMX2) potently restricts EIAV in vitro. Additionally, eMX2 inhibits HIV-1 and other lentiviruses, including murine leukemia virus. Previously, it was reported that hMXB repression is reduced in hMXB Δ1-25, but not in GTP-binding mutant K131A and GTP-hydrolysis mutant T151A. In contrast to this phenomenon, our study indicates that eMX2 restriction is not diminished in eMX2 Δ1-25, but is in eMX2 K127A and T147A, which correspond to hMXB K131A and T151A, respectively. Thus, eMX2 may inhibit retroviral replication by a novel mechanism that differs from that of hMXB.