PMID- 28179532 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20230802 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 91 IP - 9 DP - 2017 May 1 TI - A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion. LID - 10.1128/JVI.02463-16 [doi] LID - e02463-16 AB - The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4(+) T cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By next-generation sequencing of infected tissue homogenates, we assembled a contiguous 174-kb genome sequence containing 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV-6A, HHV-6B, and HHV-7, than to another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV-6A, HHV-6B, and HHV-7.IMPORTANCE Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesviruses 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and clinical ramifications of roseolovirus infection in humans have been hypothesized, but studies showing definitive causative relationships between infection and disease susceptibility are lacking. Here we show that MRV infects the thymus and causes T-cell depletion, suggesting that other roseoloviruses may have similar properties. CI - Copyright (c) 2017 American Society for Microbiology. FAU - Patel, Swapneel J AU - Patel SJ AUID- ORCID: 0000-0001-6088-4029 AD - Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Zhao, Guoyan AU - Zhao G AD - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Penna, Vinay R AU - Penna VR AD - Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Park, Eugene AU - Park E AD - Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Lauron, Elvin J AU - Lauron EJ AD - Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Harvey, Ian B AU - Harvey IB AD - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Beatty, Wandy L AU - Beatty WL AD - Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Plougastel-Douglas, Beatrice AU - Plougastel-Douglas B AD - Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Poursine-Laurent, Jennifer AU - Poursine-Laurent J AD - Howard Hughes Medical Institute, St. Louis, Missouri, USA. FAU - Fremont, Daved H AU - Fremont DH AD - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. AD - Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Wang, David AU - Wang D AD - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. AD - Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Yokoyama, Wayne M AU - Yokoyama WM AUID- ORCID: 0000-0002-0566-7264 AD - Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA yokoyama@dom.wustl.edu. AD - Howard Hughes Medical Institute, St. Louis, Missouri, USA. LA - eng GR - F30 DK108472/DK/NIDDK NIH HHS/United States GR - T32 GM007200/GM/NIGMS NIH HHS/United States GR - T34 GM008200/GM/NIGMS NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States GR - T32 AI007172/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170413 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (DNA, Viral) SB - IM CIN - J Virol. 2017 Aug 24;91(18):. PMID: 28839087 CIN - J Virol. 2017 Aug 24;91(18):. PMID: 28839089 MH - Animals MH - Base Sequence MH - CD4-Positive T-Lymphocytes/cytology/immunology MH - CD8-Positive T-Lymphocytes/cytology/immunology MH - DNA, Viral/genetics MH - *Disease Models, Animal MH - Genome, Viral/genetics MH - Herpesviridae/*classification MH - Herpesvirus 6, Human/*genetics MH - Herpesvirus 7, Human/*genetics MH - Humans MH - Immune Evasion/genetics/immunology MH - Lymphocyte Count MH - *Lymphocyte Depletion MH - Mice MH - Mice, Inbred BALB C MH - Open Reading Frames/genetics MH - Phylogeny MH - Roseolovirus Infections/*virology MH - Sequence Analysis, DNA MH - Thymus Gland/virology PMC - PMC5391440 OTO - NOTNLM OT - herpesviruses OT - roseolovirus EDAT- 2017/02/10 06:00 MHDA- 2017/05/16 06:00 PMCR- 2017/10/13 CRDT- 2017/02/10 06:00 PHST- 2017/01/03 00:00 [received] PHST- 2017/01/26 00:00 [accepted] PHST- 2017/02/10 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2017/02/10 06:00 [entrez] PHST- 2017/10/13 00:00 [pmc-release] AID - JVI.02463-16 [pii] AID - 02463-16 [pii] AID - 10.1128/JVI.02463-16 [doi] PST - epublish SO - J Virol. 2017 Apr 13;91(9):e02463-16. doi: 10.1128/JVI.02463-16. Print 2017 May 1.