title: The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting.
abstract: Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234-474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection.
authors.affiliation: Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, TX, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Hornig
authors.affiliation: Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, TX, United States.
authors.forename: K Yeon
authors.initials: KY
authors.lastname: Choi
authors.affiliation: Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, TX, United States. Electronic address: mcgregor@medicine.tamhsc.edu.
authors.forename: Alistair
authors.initials: A
authors.lastname: McGregor
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000821:virology; D003001:Cloning, Molecular; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology; D055786:Gene Knockout Techniques; D006168:Guinea Pigs; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology; D053612:Janus Kinases / Q000378:metabolism / Q000494:pharmacology; D009570:Nitriles; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines; D019211:Roseolovirus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: C094297:CALCOCO2 protein, human; C088645:IE1 protein, cytomegalovirus; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D007370:Interferon Type I; D009570:Nitriles; D009687:Nuclear Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D015534:Trans-Activators; C540383:ruxolitinib; D053612:Janus Kinases
keywords: Congenital HCMV; Daxx; Guinea pig CMV; HSV-1; Immediate-early 1; Innate immunity; Interferon; JAK-STAT; Nuclear domain 10; PML