Is murine gammaherpesvirus-68 (MHV-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence?

Aligo, Jason; Walker, Mindi; Bugelski, Peter J.; Weinstock, Daniel

doi:10.3109/1547691x.2014.882996

Cited by 10 publications

(8 citation statements)

References 157 publications

(199 reference statements)

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“…We have previously discussed how the MHV-68 model may be of further use for testing the effects of immunomodulatory compounds on viral recrudescence (Aligo et al, 2014). The focus of this report was to first establish assays for examination of MHV-68 infection.…”

Section: Discussionmentioning

confidence: 99%

“…Direct small animal models to examine these human viruses do not exist, indicating a need for better understanding of gammaherpesvirus pathogenesis. Murine gammaherpesvirus-68 (MHV-68) may be a relevant model for studying gammaherpesvirus pathogenesis as it relates to human disease (Aligo et al, 2014). However, in vivo models to examine these areas have yet to be fully characterized and an understanding of the mechanism of viral transmission in animal populations is lacking.…”

Section: Introductionmentioning

confidence: 99%

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Murine gammaherpesvirus-68 (MHV-68) is not horizontally transmitted amongst laboratory mice by cage contact

Aligo

Brosnan

Walker

et al. 2014

Journal of Immunotoxicology

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Murine gammaherpesvirus-68 (MHV-68), a natural pathogen of mice, is being evaluated as a model of Epstein Barr Virus (EBV) infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogenesis in humans. Immunosuppressive agents are used for treatment of a variety of autoimmune diseases as well as for prevention of tissue rejection after organ transplantation and can result in recrudescence of latent herpesvirus infections. Prior to examination of MHV-68 as a suitable model for EBV, better characterization of the MHV-68 model was desirable. Characterization of the MHV-68 model involved development of assays for detecting virus and for demonstration of safety when present in murine colonies. Limited information is available in the literature regarding MHV-68 transmission, although recent reports indicate the virus is not horizontally spread in research facilities. To further determine transmission potential, immunocompetent and immunodeficient mice were infected with MHV-68 and co-habitated with naïve animals. Molecular pathology assays were developed to characterize the MHV-68 model and to determine viral transmission. Horizontal transmission of virus was not observed from infected animals to naïve cagemates after fluorescence microscopy assays and quantitative PCR (qPCR). Serologic analysis complemented these studies and was used as a method of monitoring infection amongst murine colonies. Overall, these findings demonstrate that MHV-68 infection can be controlled and monitored in murine research facilities, and the potential for unintentional infection is low.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Murine gammaherpesvirus-68 (MHV-68) is not horizontally transmitted amongst laboratory mice by cage contact

Aligo

Brosnan

Walker

et al. 2014

Journal of Immunotoxicology

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“…Using recombinant MHV-68 is also a highly suitable model to test the immunogenicity and protective capacity of HCV candidate vaccine antigens (El-Gogo et al, 2008). Very important is the use of MHV-68 as immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence (Aligo et al, 2015b). MHV-68 is being evaluated as a model of EBV infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogen-esis in humans (Aligo et al, 2015a).…”

Section: Genome Of Mhv-68mentioning

confidence: 99%

Murid herpesvirus 4 (MuHV-4, prototype strain MHV-68) as an important model in global research of human oncogenic gammaherpesviruses

Mistríková¹,

Briestenská²

2020

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The aim of this work was to give an overview of murid herpesvirus 4 (MuHV-4) (synonyms: murine gammaherpesvirus 68, mouse herpesvirus strain 68), the first model for the study of human and animal oncogenic gammaherpesviruses. Based on our results confirming similarity of murine gammaherpesvirus 68 (MHV-68) to another gammaherpesvirus, human oncogenic Epstein-Barr virus (EBV), we were able to interpret some processes observed in the course of MHV-68 infection in analogy to EBV infection. In particular, that were the processes occurring during MHV-68-induced persistent infection in mice accompanied by tumor formation and leukemia following immunosuppression. Since EBV is a highly species specific virus, infecting humans only, these processes cannot be experimentally examined at the molecular, cellular, and tissue levels in natural host. However, they can be investigated in BALB/c mice infected with MHV-68, which is nowadays generally accepted model mainly thanks to experimental results achieved by our research team. The important mouse model MHV-68 is a prototype strain of MuHV-4 species and is classified as a member of the order Herpesvirales, family Herpesviridae, subfamily Gammaherpesvirinae and genus Rhadinovirus. During 40 years since its isolation from wild rodents, the virus was distributed into many virological laboratories in Europe (such as England,

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“…While murine herpesvirus-68 (MHV-68) is a natural pathogen of rodents, the pathogenesis of MHV-68 infection in mice mimics that of EBV/KSHV infection in humans with acute lytic viral replication, followed by the dissemination and establishment of persistent latency [79].…”

Section: Murine Herpesvirus-68-encoded Lncrnasmentioning

confidence: 99%

The Structure-To-Function Relationships of Gammaherpesvirus-Encoded Long Non-Coding RNAs and Their Contributions to Viral Pathogenesis

Chávez-Calvillo

Martin

Hamm

et al. 2018

ncRNA

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Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease, and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. These lncRNAs allow for the virus to escape cytosolic surveillance, sequester, and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis, and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.

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Is murine gammaherpesvirus-68 (MHV-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence?

Cited by 10 publications

References 157 publications

Murine gammaherpesvirus-68 (MHV-68) is not horizontally transmitted amongst laboratory mice by cage contact

Murine gammaherpesvirus-68 (MHV-68) is not horizontally transmitted amongst laboratory mice by cage contact

Murid herpesvirus 4 (MuHV-4, prototype strain MHV-68) as an important model in global research of human oncogenic gammaherpesviruses

The Structure-To-Function Relationships of Gammaherpesvirus-Encoded Long Non-Coding RNAs and Their Contributions to Viral Pathogenesis

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