Study On The Mechanism Of Host Factor MOV10 Inhibiting XMRV Replication

Xenotropic murine leukemia virus-related virusis (XMRV) is a novel replication-competent virus which belongs to gammaretrovious. In the previous studies, It was reported that XMRV might be associated with human diseases of prostate cancer and chronic fatigue syndrome (CFS), but in recent studies, it was shown that they failed to identify XMRV in prostate cancer tissues and CFS patients’samples, even in the early samples in which XMRV was detected they failed to find XMRV, they thought that the early results was caused by experimental contamination, excluded the relationship between XMRV and these two human diseases. Finally, the assertion that XMRV is circulating in human population has been challenged by the report showing that XMRV was generated by a recombination event between two endogenous MLVs during in vivo tumor passaging in mice, which yielded the popular prostate cancer cell line22Rvl. Although the associations of the XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells in vitro. And XMRV has the properties of gammaretrovious, it can be used as a model virus in the researches which study the interactions between host factors and retroviruses. It was reported that there were some inhibitors in host cells that could inhibit XMRV, such as Human APOBEC3and Tetherin and so on.Moloney leukemia virus10(MOV10) is a kind of host factor. It is widely expressed in the human, mouse and other species, and in a variety of cell types, including embryonic stem cells. MOV10protein is a superfamily-1RNA helicase, and it is also a component of the RNA-induced silencing complex. Recent studies had shown that MOV10had a broad antiretroviral activity that could target a wide range of retroviruses including HIV-1, and MOV10played an active role in the RNA interference pathway. MOV10has seven conserved motifs about Helicases. These seven conserved motifs play important roles in the antiretroviral activity of MOV10.The contents of this study were as follows, studied the inhibition of MOV10on XMRV replication and inhibition mechanism, found the key areas which played important roles in the antiretroviral activity of MOV10. our study have certain innovation.In this study, we cotransfected the Mammalian cells with XMRV proviral DNA and MOV10plasmid/MOV10mutants, then the producted virus infected cells, Finally the viral infectivity was detected. From the methods above we could study the inhibition of MOV10on XMRV replication and inhibition mechanism, find the key areas which played important roles in the antiretroviral activity of MOV10. Through this study we got the following conclusions:MOV10inhibited XMRV replication. When it was overexpressed in viral producer cells, MOV10was able to reduce the infectivity of XMRV. Conversely, when endogenous MOV10expression was reduced by small interfering RNAs, XMRV infectivity was increased. Furthermore, we found that MOV10could be packaged into virions. It blocked XMRV replication at a postentry step. These seven conserved motifs played important roles in the antiretroviral activity of MOV10. in which motif Ⅰ,Ⅱ,Ⅲand Ⅳ were the most important, motif VandVI secondly, motif la was the least critical.The results of this study prove MOV10can inhibit the XMRV which belongs to gammaretrovious replication, preliminarily clarify the inhibition mechanism, preliminarily find the key areas which play important roles in the antiretroviral activity of MOV10. our study Further confirm that MOV10has a broad antiretroviral activity that can target a wide range of retroviruses, and it could be actively involved in host defense against retroviral infection.