the dead-box rna helicase ddx6 is required for efficient encapsidation of a retroviral genome出局区rna解旋酶ddx6需要有效的衣壳化逆转录病毒基因组.pdfVIP

The DEAD-box RNA Helicase DDX6 is Required for Efficient Encapsidation of a Retroviral Genome 1 1¤ 1 2 1 Shuyuarn F. Yu , Phillip Lujan , Dana L. Jackson , Michael Emerman , Maxine L. Linial * 1 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 2 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America Abstract Viruses have to encapsidate their own genomes during the assembly process. For most RNA viruses, there are sequences within the viral RNA and virion proteins needed for high efficiency of genome encapsidation. However, the roles of host proteins in this process are not understood. Here we find that the cellular DEAD-box RNA helicase DDX6 is required for efficient genome packaging of foamy virus, a spumaretrovirus. After infection, a significant amount of DDX6, normally concentrated in P bodies and stress granules, re-localizes to the pericentriolar site where viral RNAs and Gag capsid proteins are concentrated and capsids are assembled. Knockdown of DDX6 by siRNA leads to a decreased level of viral nucleic acids in extracellular particles, although viral protein expression, capsid assembly and release, and accumulation of viral RNA and Gag protein at the assembly site are little affected. DDX6 does not interact stably with Gag proteins nor is it incorporated into particles. However, we find that the ATPase/helicase motif of DDX6 is essential for viral replication. This suggests that the ATP hydrolysis and/or the RNA unwinding activities of DDX6 function in moderating the viral RNA conformation and/or viral RNA-Gag ribonucleoprotein complex in a transient manner to facilitate incor