The Restriction Mechanism Of Equine Interferon Induced Mx2 To Lentivirus

Myxovirus resistance proteins II(Mx2)belongs to the Myxovirus resistance(Mx)family.MxA protein has long been recognized as a key interferon-inducible intracellular restriction effector and a marker gene for interferon action and suppresses a wide range of DNA and RNA viruses.Mx2,however,was always thought to lack antiviral activity,and instead to contribute to certain basic cell functions,such as regulating nucleocytoplasmic transport and cell-cycle progression.The antiviral activity of MxB was first reported in 2013,when it was shown that human MxB protein plays a crucial role in blocking HIV-1 infection in interferon-induced human cells.Human Myxovirus resistance 2(huMxB)has been shown to be a determinant type I interferon induced host factor involved in the inhibition of HIV-1 as well as many other primate lentiviruses.The block is closely connected with its nuclear envelope localization and its N-terminus viral capsid binding ability,which may block the nuclear uptake of viral DNA.To date,human MxB protein shows little or no ability to limit nonprimate lentivirus infection.Meanwhile,Mx2 s from many other non-human primates has also been reported to inhibit infection of HIV-1,whereas Mx2 from other mammals(ovine and canine)lack this function.So far,there have been no reports of antiviral activity in non-primate Mx2 proteins,including that from equine infectious anemia virus(EIAV).Mx2 s derived from nonprimate animals have shown no capacity for HIV-1 suppression.In this study,we examined the restrictive effect of equine Mx2(eqMx2)on both the equine infectious anemia virus(EIAV),SIVs,and HIV-1,and investigated possible mechanisms for its specific function.We demonstrate that IFN?/? upregulates the expression of eqMx2 in equine monocyte-derived macrophages(eMDMs).Overexpression of eqMx2 significantly suppresses the replication of EIAV,HIV-1,and SIVs,but not MLV.Knockdown of eqMx2 transcription weakens the inhibition of EIAV replication by type I interferon.Interestingly,immunofluorescence assays found that eqMx2 changes its subcellular localization from being dispersed in the cytoplasm to being accumulated at the nuclear envelope following virus infection.Furthermore,eqMx2 blocks the nuclear uptake of proviral genome by binding to the viral capsid.The N-truncated mutant has lost both the ability to bind the viral capsid and the restriction effect for lentiviruses.This research firstly proved that equine Mx2 can suppress the infection of EIAV as well as HIV-1 and SIV.It prompts that as an innate immunity interspecies restriction factor,equine Mx2 plays an important role in the evolution of species innate immunity.These results improve our understanding of the Mx2 protein in nonprimate animals.