Maul GG, Everett RD. 1994. deletion of the gene encoding the immediate-early ICP0 protein. Additionally, a deletion of the gene encoding the tegument protein Vhs ablated most of the depletion of ATRX mRNA. Thus, HSV is equipped with multiple mechanisms to limit the expression Methyl Hesperidin of ATRX. As ATRX is implicated in repression of lytic viral gene expression, our results suggest roles for these different mechanisms during various phases of HSV infection. INTRODUCTION Hosts have evolved a myriad of mechanisms to control infection by viruses, while viruses have evolved counteracting mechanisms, often redundant, to prevail. The adaptive and innate immune systems, which require complex signaling pathways to activate and mobilize their effectors, can effectively control virus infection. Recently, the concept of intrinsic immunity (also called intrinsic antiviral defense) has emerged. Intrinsic immunity provides an immediate antiviral defense Methyl Hesperidin mediated by Methyl Hesperidin constitutively expressed factors whose activity does not depend on a signaling cascade (reviewed in references 6 and 98). One set of such host factors includes proteins organized within discrete nuclear substructures known as nuclear domain 10 (ND10; also called promyelocytic leukemia protein [PML] nuclear bodies) that repress the initial transcription of herpesviruses (1, 9, 24, 50, 51, 64, 69, 70, 85C88, 96). ND10s harbor multiple cellular proteins, including PML, speckled protein of 100 kDa (Sp100), death domain-associated protein (hDaxx), and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) protein (34, 58). Of these, ATRX is a member of the switch 2, sucrose nonfermenting 2 (SWI2/SNF2) family of helicases/ATPases. Mutations in the gene are associated with an X-linked mental retardation and alpha-thalassemia syndrome (63). ATRX, like other members of the SWI2/SNF2 family, is involved in different biological processes, including transcription regulation, cell cycle regulation, and mitotic chromosome segregation (reviewed in references 11 and 63) and chromatin remodeling (27, 94). ATRX forms a chromatin-remodeling complex with hDaxx (81, 97). It is involved in the deposition of the H3.3 histone variant at telomeres, and it is important for telomere integrity and for repression of gene expression at telomeres (17, 28, 31, 48, 95). ATRX also associates with several other chromatin factors involved in transcriptional repression, such as heterochromatin protein 1a (HP1a) (55), a nonhistone component of chromatin, and EZH2 (10), a member of the polycomb group family. During herpesvirus infections, ND10 constituents are recruited to novel ND10 Methyl Hesperidin structures that localize adjacent to incoming parental Prom1 herpesvirus genomes (21, 25). Subsequently, this association and ND10 integrity are disrupted. In the case of herpes simplex virus 1 (HSV-1), the disruption entails the activity of the immediate early (IE) protein ICP0, which is required for the dispersal of ND10 proteins, including ATRX, and the degradation of PML and Sp100 (7, 12, 50, 53, 54, 59, 61). In cells infected with ICP0-null viruses, replication is impaired and ND10 structures associate with the viral genomes much longer (20, 68, 77). It has been proposed that this association generates a repressive environment for viral transcription due to the activity of ND10 components. Consistent with this concept, replication of ICP0-null viruses can be partially rescued in cells depleted of PML, Sp100, hDaxx, or ATRX (23, 24, 50). Like many other herpesviruses, HSV-1 and HSV-2 express numerous microRNAs (miRNAs), some of which are conserved between these two viruses (15, 38, 82C84, 91C93). Thus far, only a few targets of HSV miRNAs have been identified, and most of these are encoded from the strand opposite of that of an miRNA and thus are entirely complementary to the miRNA (37, 83, 84, 91). HSV-1 miR-H1, the first HSV miRNA discovered, is expressed abundantly during productive (lytic) infection (15, 38, 42, 91, 92). Interestingly, no positional homolog of HSV-1 miR-H1 has been detected in Methyl Hesperidin HSV-2-infected cells. Nonetheless, the seed sequence of HSV-2 miR-H6 (the positional homolog of HSV-1 miR-H6, which is encoded complementary to HSV-1 miR-H1), is identical to the seed sequence of HSV-1 miR-H1,.