A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion.
The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise theRoseolovirusgenus of the humanBetaherpesvirinaesubfamily. 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.IMPORTANCEHerein 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.
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Swapneel J
http://orcid.org/0000-0001-6088-4029
SJ
Patel
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Guoyan
G
Zhao
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Vinay R
VR
Penna
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Eugene
E
Park
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Elvin J
EJ
Lauron
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Ian B
IB
Harvey
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Wandy L
WL
Beatty
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Beatrice
B
Plougastel-Douglas
Howard Hughes Medical Institute, St. Louis, Missouri, USA.
Jennifer
J
Poursine-Laurent
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, USA.
Daved H
DH
Fremont
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
David
D
Wang
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA yokoyama@dom.wustl.edu.|Howard Hughes Medical Institute, St. Louis, Missouri, USA.
Wayne M
http://orcid.org/0000-0002-0566-7264
WM
Yokoyama
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D016679:Genome, Viral / Q000235:genetics; D006564:Herpesviridae / Q000145:classification*; D015654:Herpesvirus 6, Human / Q000235:genetics*; D016199:Herpesvirus 7, Human / Q000235:genetics*; D006801:Humans; D057131:Immune Evasion / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D019349:Roseolovirus Infections / Q000821:virology*; D017422:Sequence Analysis, DNA; D013950:Thymus Gland / Q000821:virology
D004279:DNA, Viral
herpesviruses; roseolovirus