Human cytomegalovirus evades ZAP detection by suppressing CpG dinucleotides in the major immediate early 1 gene

The genomes of RNA and small DNA viruses of vertebrates display significant suppression of CpG dinucleotide frequencies. Artificially increasing dinucleotide frequencies results in substantial attenuation of virus replication, suggesting that these compositional changes may facilitate recognition of non-self RNA sequences. Recently, the interferon inducible protein ZAP, was identified as the host factor responsible for sensing CpG in viral RNA, through direct binding and possibly downstream targeting for degradation. Using an arrayed interferon stimulated gene expression library screen, we identified ZAPS, and its associated factor TRIM25, as inhibitors of human cytomegalovirus (HCMV) replication. Exogenous expression of ZAPS and TRIM25 significantly reduced virus replication while knockdown resulted in increased virus replication. HCMV displays a strikingly heterogeneous pattern of CpG representation with specific suppression of CpG motifs within the IE1 major immediate early transcript which is absent in subsequently expressed genes. We demonstrated that suppression of CpG dinucleotides in the IE1 gene allows evasion of inhibitory effects of ZAP. We show that acute virus replication is mutually exclusive with high levels of cellular ZAP, potentially explaining the higher levels of CpG in viral genes expressed subsequent to IE1 due to the loss of pressure from ZAP in infected cells. Finally, we show that TRIM25 regulates alternative splicing between the ZAP short and long isoforms during HCMV infection and interferon induction, with knockdown of TRIM25 resulting in decreased ZAPS and corresponding increased ZAPL expression. These results demonstrate for the first time that ZAP is a potent host restriction factor against large DNA viruses and that HCMV evades ZAP detection through suppression of CpG dinucleotides within the major immediate early 1 transcript. Furthermore, TRIM25 is required for efficient upregulation of the interferon inducible short isoform of ZAP through regulation of alternative splicing

Guide to Agriculture, U.S.A.

The purpose of the Guide is to introduce the reader to agriculture in the United States. Here will be found the general facts about the land and how it is used, the major crops and where they are grown, and the principal livestock products. Especial attention is given to farm families, where they live, how they do their work, and the way they help determine public policy as it affects agriculture. The Guide is prepared primarily for foreign visitors. It is hoped, however, that it will prove helpful also to citizens of the United States

A study of Negro life in Tampa : made at the request of The Tampa Welfare League, The Tampa Urban League and the Tampa Young Men\u27s Christian Association.

https://digitalcommons.usf.edu/regional_ebooks/1037/thumbnail.jp

A study of Negro life in Tampa : made at the request of The Tampa Welfare League, The Tampa Urban League and the Tampa Young Men\u27s Christian Association.

https://digitalcommons.usf.edu/regional_ebooks/1037/thumbnail.jp

The tragedy of lynching /

Presented by the Southern Commission on the Study of Lynching

Environmental capacity and European air transport: Stakeholder opinion and implications for modelling

This paper reports on a survey of stakeholder views on airport environmental capacity, commissioned by EUROCONTROL. The survey found divergent opinion on the role of environmental limits in conceptions of environmental capacity. While there is widespread agreement that environmental constraints are likely to prove increasingly problematic for European aviation, there is also a wide range of opinion regarding institutional aspects of their management