B cells latently infected with murine gammaherpesvirus 68 (MHV‐68) are present in the mouse thymus–A step toward immune evasion?

Yamano, Tomoyoshi; Steinert, Madlen; Steer, Beatrix; Klein, Ludger; Hammerschmidt, Wolfgang; Adler, Heiko

doi:10.1002/eji.201847886

Eur J Immunol

2018

DOI: 10.1002/eji.201847886

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B cells latently infected with murine gammaherpesvirus 68 (MHV‐68) are present in the mouse thymus–A step toward immune evasion?

Tomoyoshi Yamano

Madlen Steinert

Beatrix Steer

et al.

Abstract: We show that latently gammaherpesvirus‐infected B cells are present in the thymus. This could result in a functional T‐cell tolerance against certain viral epitopes. It is conceivable that also antigens from other viruses or pathogens may be conveyed to the thymus for their immune evasion.

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Cited by 3 publications

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“…Sites of latency of other γHVs are primarily associated with B cells and sometimes macrophages or dendritic cells of lymphoid tissues in the spleen, thymus, and bone marrow. 68,71,75 Although these are the major sites of latency, this viral state has also been reported in the lung of experimentally infected laboratory mice using murine herpesvirus 4. 30 However, pulmonary intravascular macrophages (PIMs), which are found within the lung of other species, are absent in rodents.…”

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confidence: 97%

Tissue and cellular tropism of Eptesicus fuscus gammaherpesvirus in big brown bats, potential role of pulmonary intravascular macrophages

Perdrizet,

Hill,

Sobchishin

et al. 2024

Vet Pathol

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Gammaherpesviruses (γHVs) are recognized as important pathogens in humans but their relationship with other animal hosts, especially wildlife species, is less well characterized. Our objectives were to examine natural Eptesicus fuscus gammaherpesvirus (EfHV) infections in their host, the big brown bat ( Eptesicus fuscus), and determine whether infection is associated with disease. In tissue samples from 132 individual big brown bats, EfHV DNA was detected by polymerase chain reaction in 41 bats. Tissues from 59 of these cases, including 17 from bats with detectable EfHV genomes, were analyzed. An EfHV isolate was obtained from one of the cases, and electron micrographs and whole genome sequencing were used to confirm that this was a unique isolate of EfHV. Although several bats exhibited various lesions, we did not establish EfHV infection as a cause. Latent infection, defined as RNAScope probe binding to viral latency-associated nuclear antigen in the absence of viral envelope glycoprotein probe binding, was found within cells of the lymphoid tissues. These cells also had colocalization of the B-cell probe targeting CD20 mRNA. Probe binding for both latency-associated nuclear antigen and a viral glycoprotein was observed in individual cells dispersed throughout the alveolar capillaries of the lung, which had characteristics of pulmonary intravascular macrophages. Cells with a similar distribution in bat lungs expressed major histocompatibility class II, a marker for antigen presenting cells, and the existence of pulmonary intravascular macrophages in bats was confirmed with transmission electron microscopy. The importance of this cell type in γHVs infections warrants further investigation.

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mentioning

confidence: 97%

Tissue and cellular tropism of Eptesicus fuscus gammaherpesvirus in big brown bats, potential role of pulmonary intravascular macrophages

Perdrizet,

Hill,

Sobchishin

et al. 2024

Vet Pathol

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Conquering the Host: Determinants of Pathogenesis Learned from Murine Gammaherpesvirus 68

2021

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Gammaherpesviruses are an important class of oncogenic pathogens that are exquisitely evolved to their respective hosts. As such, the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV) do not naturally infect nonhuman primates or rodents. There is a clear need to fully explore mechanisms of gammaherpesvirus pathogenesis, host control, and immune evasion in the host. A gammaherpesvirus pathogen isolated from murid rodents was first reported in 1980; 40 years later, murine gammaherpesvirus 68 (MHV68, MuHV-4, γHV68) infection of laboratory mice is a well-established pathogenesis system recognized for its utility in applying state-of-the-art approaches to investigate virus-host interactions ranging from the whole host to the individual cell. Here, we highlight recent advancements in our understanding of the processes by which MHV68 colonizes the host and drives disease. Lessons that inform KSHV and EBV pathogenesis and provide future avenues for novel interventions against infection and virus-associated cancers are emphasized.

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The innate and T-cell mediated immune response during acute and chronic gammaherpesvirus infection

Rex

Zargari

Stempel

et al. 2023

Front. Cell. Infect. Microbiol.

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Immediately after entry into host cells, viruses are sensed by the innate immune system, leading to the activation of innate antiviral effector mechanisms including the type I interferon (IFN) response and natural killer (NK) cells. This innate immune response helps to shape an effective adaptive T cell immune response mediated by cytotoxic T cells and CD4+ T helper cells and is also critical for the maintenance of protective T cells during chronic infection. The human gammaherpesvirus Epstein-Barr virus (EBV) is a highly prevalent lymphotropic oncovirus that establishes chronic lifelong infections in the vast majority of the adult population. Although acute EBV infection is controlled in an immunocompetent host, chronic EBV infection can lead to severe complications in immunosuppressed patients. Given that EBV is strictly host-specific, its murine homolog murid herpesvirus 4 or MHV68 is a widely used model to obtain in vivo insights into the interaction between gammaherpesviruses and their host. Despite the fact that EBV and MHV68 have developed strategies to evade the innate and adaptive immune response, innate antiviral effector mechanisms still play a vital role in not only controlling the acute infection but also shaping an efficient long-lasting adaptive immune response. Here, we summarize the current knowledge about the innate immune response mediated by the type I IFN system and NK cells, and the adaptive T cell-mediated response during EBV and MHV68 infection. Investigating the fine-tuned interplay between the innate immune and T cell response will provide valuable insights which may be exploited to design better therapeutic strategies to vanquish chronic herpesviral infection.

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B cells latently infected with murine gammaherpesvirus 68 (MHV‐68) are present in the mouse thymus–A step toward immune evasion?

Cited by 3 publications

References 9 publications

Tissue and cellular tropism of Eptesicus fuscus gammaherpesvirus in big brown bats, potential role of pulmonary intravascular macrophages

Tissue and cellular tropism of Eptesicus fuscus gammaherpesvirus in big brown bats, potential role of pulmonary intravascular macrophages

Conquering the Host: Determinants of Pathogenesis Learned from Murine Gammaherpesvirus 68

The innate and T-cell mediated immune response during acute and chronic gammaherpesvirus infection

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