Mouse thymic virus (MTLV). A mammalian herpesvirus cytolytic for CD4+ (L3T4+) T lymphocytes.

Morse, Stephen S.; Valinsky, Jay E.

doi:10.1084/jem.169.2.591

Cited by 18 publications

(10 citation statements)

References 14 publications

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“…1A and B). Depletion was evident in the CD4 ϩ single positive (CD4 SP) subsets in the thymus, as previously reported for MTV (20). We observed reductions in double positive (CD4 ϩ CD8 ϩ , DP) thymocytes, and both major T-cell subsets (CD4 ϩ and CD8 ϩ ) in the spleen.…”

Section: Resultssupporting

confidence: 62%

“…Herein we showed that MRV inoculation in the peritoneum results in MRV expansion in the thymus, as determined by our genome copy number assay. We found depletion of thymocyte subsets, suggesting lytic infection of T cells (20). Our study shows that MRV is also detectable at lower levels in peripheral organs of the mouse after acute infection, though this could be related to infected T-cell spread to these organs or viremia rather than direct infection of these organs.…”

Section: Discussionmentioning

confidence: 56%

“…Blind passage of pooled organs from adult mice into neonatal mice by intraperitoneal injection reproducibly led to thymic "necrosis" in infected mice. Subsequent reports indicate that MTV infection of neonates leads to depletion of CD4 ϩ T cells in the thymus of infected animals, whereas adult infections appear to be subclinical, with elevation of anti-MTV antibody titers but no overt thymic pathology (20,36,37). Neonatal depletion of CD4 ϩ T cells is transient, as by 6 weeks postinfection, mice appear to have recovered a normal complement of CD4 ϩ T cells in the spleen and thymus (38).…”

Section: Discussionmentioning

confidence: 99%

“…Given the incomplete passage history and source of the virus stocks, we were unable to verify that this virus was directly linked to the originally described MTV (19). Virus stocks were produced by in vivo passaging as previously described (20,38). A single virus stock was used for all experiments.…”

Section: Methodsmentioning

confidence: 99%

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A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion

Patel

Zhao

Penna

et al. 2017

J Virol

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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 ϩ 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.KEYWORDS herpesviruses, roseolovirus T he study of herpesviruses has been fruitful, not only revealing mechanisms that drive disease but also providing insight into diverse processes, including oncogenesis and immune regulation (1). The Herpesviridae family includes several highly prevalent human pathogens (1-3). While they are related, these viruses have diverse genomes,

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Section: Resultssupporting

confidence: 62%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion

Patel

Zhao

Penna

et al. 2017

J Virol

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“…Viral stocks were produced by in vivo passaging as previously described (18, 23, 25). A single viral stock was used for all experiments.…”

Section: Methodsmentioning

confidence: 99%

CD8+ T Cells Prevent Lethality from Neonatal Murine Roseolovirus Infection

Patel

Yokoyama

2017

The Journal of Immunology

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A recently described mouse homolog of the human roseoloviruses, murine roseolovirus (MRV), causes loss of peripheral and thymic CD4+ cells during neonatal infection of BALB/c mice. Despite significant disruptions to the normal adaptive immune response, infected BALB/c mice reproducibly recover from infection, consistent with prior studies on a related virus, mouse thymic virus (MTV). Herein we show that in contrast to published studies on MTV, MRV appears to robustly infect neonatal C57BL/6 (B6) mice causing severe depletion of thymocytes and peripheral T-cells. Moreover, B6 mice recovered from infection. We investigated the mechanism of thymocyte and T-cell loss, determining that the major thymocyte subsets were infected with MRV, however CD4+ and CD4+CD8− showed increased apoptosis during infection. We found that CD8+ T-cells populated MRV-infected thymi. These CD8+ T cells expressed markers of activation, had restricted T-cell receptor repertoire and accumulated intracellular effector proteins, consistent with a cytotoxic lymphocyte phenotype, and suggesting their involvement in viral clearance. Indeed, absence of CD8+ T-cells prevented recovery from MRV infection and led to lethality in infected animals whereas B-cell deficient mice showed CD4+ T-cell loss but recovered from infection without lethality. Thus these results demonstrate that CD8+ T-cells are required for protective immunity against a naturally occurring murine pathogen that infects the thymus, and establish a novel infection model for MRV in B6 mice, providing the foundation for detailed future studies on MRV with the availability of innumerable mutant mice on the B6 background.

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Mouse

Percy¹,

Barthold

2007

Pathology of Laboratory Rodents and Rabbits

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The laboratory mouse is an artificial creation, and there is no true "wildtype" laboratory mouse. Furthermore, there is no such thing as "normal" microflora, since laboratory mice are maintained in microbially pristine environments devoid of pathogens and opportunistic pathogens, as well as other commensal flora/fauna. House mice, from which laboratory mice originated, are represented by several species and subspecies native to the Old World. Laboratory mice are largely derived from domesticated "fancy mice" that arose from many years of trading of mouse variants among fanciers in Europe, Asia, North America, and Australia. The laboratory mouse genome, including its retroelements, is a mosaic derived from different subspecies of the Mus musculus complex, including M.m. domesticus, M.m. musculus, M.m. castaneus, M.m. molossinus (a natural hybrid of M.m. musculus and M.m. castaneus), and M. bactrianus.The genome of M.m. domesticus is the predominant contributor to most strains of mice, but many inbred strains share a common "Eve" with a mitochondrial genome of M.m. musculus origin, and a common "Adam" that contributed their Y chromosome from Asian mice. In addition, there is evidence that other Mus species, outside of the M. musculus complex, may have contributed to the genome of some laboratory mouse strains. The C57BL mouse genome contains a contribution from M. spretus. The 1st inbred mouse (DBA), and other strains with DBA genetic contributions, was partially derived from Japanese waltzing mice with M. bactrianus parentage. Perhaps the only laboratory mouse that is derived from a single species (subspecies), M.m. domesticus, is the "Swiss" mouse, but there is a high likelihood that several Swiss stocks and strains have been genetically corrupted.There are over 450 inbred strains of laboratory mice that have arisen during the last century, and these strains, which were selectively inbred to pan-genomic homozygosity for purposes entirely unrelated to modern research, are the foundation upon which literally thousands of spontaneous mutants and GEMs have been built. Additional inbred strains have been developed from wild mice (M.m. castaneus, M. spretus, etc.). Furthermore, "outbred" mice (mostly Swiss mice) are highly homozygous and nearly inbred. There is no such thing as an outbred laboratory mouse with a fully heterozygous genome representative of wildtype M. musculus, and there is no wild mouse genetic counterpart of the laboratory mouse. When working with mice, the pathologist must also become facile with hybrids,

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Mouse thymic virus (MTLV). A mammalian herpesvirus cytolytic for CD4+ (L3T4+) T lymphocytes.

Cited by 18 publications

References 14 publications

A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion

A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion

CD8+ T Cells Prevent Lethality from Neonatal Murine Roseolovirus Infection

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