Schematic representation of mechanisms of activation of a host gene by insertion of a provirus and the general structure of leukemia and leukosis and acute transforming retroviral genomes. A: Genome of a nondefective leukemia or leukosis retrovirus, infection of host cell, and integration into the host genome. The gag region encodes the internal structural proteins of the virion, the pol region encodes the virion RNA-dependent DNA polymerase (reverse transcriptase), and the env region encodes the proteins found on the surface of the virion envelope. long terminal repeat sequences encoding retroviral transcriptional control elements (LTR) is the long terminal repeat that appears at each end of the integrated linear DNA forms. Within the LTR region are DNA sequences, which define the initiation site for RNA transcription and at the 3′ end encode a poly A addition site where the viral RNA polyadenylation occurs and transcription enhancer sequences that result in the production of high levels of transcripts. The LTR elements provide all of the necessary functions for eukaryotic transcription to take place and for the provirus to express genomic viral RNA. B and C: Two different configurations of inserted proviral DNA. Replication competent and replication defective viruses are produced. The genome of a replication-defective acute transforming retrovirus containing v-onc sequences is shown. Although substantial portions of gag, of the retroviral gene encoding reverse transcriptase (pol), and/or of the retroviral gene encoding protein components of the virion nucleoprotein core (env) may be deleted in acute transforming retroviruses, they still retain the terminal noncoding LTR regions. B: Insertion of a proviral LTR upstream of the first coding exon as observed with c-myc. This insertion results in a transcript that no longer contains sequences that regulate c-myc expression levels. The protein-coding domains (exons) of the normal host gene are in solid black rectangles. C: Integration of an intact provirus upstream (or downstream) from, for example, the int 1 or int 2 genes. This form of integration may not alter the gene product but generally results in increased transcription of that gene promoted by the transcriptional enhancing activity of the retroviral LTR. Source: Oncogenes, The Online Metabolic and Molecular Bases of Inherited Disease Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: https://ommbid.mhmedical.com/DownloadImage.aspx?image=/data/books/971/ch25fg2.png&sec=62664161&BookID=971&ChapterSecID=62664153&imagename= Accessed: September 29, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved