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[PMID]: | 28179532 |
[Au] Autor: | Patel SJ; Zhao G; Penna VR; Park E; Lauron EJ; Harvey IB; Beatty WL; Plougastel-Douglas B; Poursine-Laurent J; Fremont DH; Wang D; Yokoyama WM |
[Ad] Endereço: | Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. |
[Ti] Título: | A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion. |
[So] Source: | J Virol;91(9), 2017 May 01. | [Is] ISSN: | 1098-5514 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the genus of the human 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. 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. |
[Mh] Termos MeSH primário: |
Modelos Animais de Doenças Herpesviridae/classificação Herpesvirus Humano 6/genética Herpesvirus Humano 7/genética Depleção Linfocítica Infecções por Roseolovirus/virologia
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[Mh] Termos MeSH secundário: |
Animais Sequência de Bases Linfócitos T CD4-Positivos/citologia Linfócitos T CD4-Positivos/imunologia Linfócitos T CD8-Positivos/citologia Linfócitos T CD8-Positivos/imunologia DNA Viral/genética Genoma Viral/genética Seres Humanos Evasão da Resposta Imune/genética Evasão da Resposta Imune/imunologia Contagem de Linfócitos Camundongos Camundongos Endogâmicos BALB C Fases de Leitura Aberta/genética Filogenia Análise de Sequência de DNA Timo/virologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (DNA, Viral) |
[Em] Mês de entrada: | 1705 |
[Cu] Atualização por classe: | 171013 |
[Lr] Data última revisão:
| 171013 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170210 |
[St] Status: | MEDLINE |
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