Murine Cytomegalovirus Virion-Associated Protein M45 Mediates Rapid NF-κB Activation after Infection

Krause, Eva; Graaf, Miranda de; Fliss, Patricia M.; Dölken, Lars; Brune, Wolfram

doi:10.1128/jvi.00684-14

Cited by 28 publications

(45 citation statements)

References 61 publications

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“…MCMV-M45HA, MCMV-M45Ct3, and the MCMV deletion mutant ⌬M45 have been described previously (33). The ⌬M36 mutant was constructed essentially in the same way as described earlier for ⌬M45 (33).…”

Section: Methodsmentioning

confidence: 99%

“…The ⌬M36 mutant was constructed essentially in the same way as described earlier for ⌬M45 (33). The substitution mutants were generated by en passant mutagenesis (36) of the MCMV Smith bacterial artificial chromosome (BAC).…”

Section: Methodsmentioning

confidence: 99%

“…For all other immunoblot analyses, cells were lysed in boiling SDS-PAGE sample buffer. Immunofluorescence staining and detection were done as described previously (33).…”

Section: Methodsmentioning

confidence: 99%

“…We previously showed that virion-associated M45 induces a rapid and transient activation of NF-B immediately after infection of fibroblasts, while de novo-synthesized M45 blocks all canonical NF-B signaling pathways (32,33). Similarly, M45 expressed transiently by plasmid transfection activates NF-B (33), whereas prolonged expression (e.g., by retroviral transduction) blocks NF-B activation (32).…”

Section: Characterization Of MCMV Mc159 Substitution Mutantsmentioning

confidence: 99%

“…Importantly, M45 redirects NEMO to autophagosomes, thereby blocking all canonical NF-B-activating pathways (32). However, M45 also mediates a brief and transient NF-B activation in fibroblasts immediately after infection: NF-B is activated during the first few hours of the infection by virion-associated M45 and inhibited at later time points by de novo-synthesized M45, suggesting an M45 concentration-dependent effect on NF-B (33).…”

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confidence: 99%

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Functional Comparison of Molluscum Contagiosum Virus vFLIP MC159 with Murine Cytomegalovirus M36/vICA and M45/vIRA Proteins

Hüttmann

Krause

Schommartz

et al. 2016

J Virol

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Molluscum contagiosum virus (MCV) gene IMPORTANCEMCV is a human-pathogenic poxvirus that cannot be propagated in cell culture or laboratory animals. Therefore, MCV gene products have been studied predominantly in cells expressing individual viral genes. In this study, we analyzed the function of the MCV gene MC159 by expressing it from a different virus and comparing its functions to those of two well-characterized MCMV genes. In this system, MC159 displayed some but not all of the previously described functions, suggesting that the functions of a viral gene depend on the conditions under which it is expressed. Until a cell culture system for the analysis of MCV becomes available, it might be necessary to analyze MCV genes in several different systems to extrapolate their biological importance. Molluscum contagiosum virus (MCV) is a worldwide-occurring poxvirus that replicates exclusively in humans (1). Seroprevalence ranges from up to 39% in immunocompetent individuals (2, 3), affecting mostly children and young adults, to 91% in HIV-infected patients (2). Molluscum contagiosum (MC) is an infectious disease of the skin characterized by small, benign papular skin lesions that usually regress after a few months. However, in immunocompromised patients MC can become much more severe, with extensive lesions that are difficult to treat (1). This indicates the important role of the host immune system in confining and eliminating the infection.Despite its importance as a human pathogen, MCV has not been studied extensively due to technical difficulties. There is neither a cell culture system suitable for the propagation of MCV nor an animal model that recapitulates MCV replication. Therefore, individual MCV genes were studied either by using transient transfection or by expression in a recombinant vaccinia virus (VACV) as a surrogate virus (4).MCV expresses several immune-modulating proteins that are thought to contribute to the persistence of the virus (4, 5). One of these proteins, MC159, has been identified as a viral FLICE-like inhibitory protein (vFLIP) (6) due to its structural and functional similarity to cellular FLIP (cFLIP) (7). Although vFLIPs have not been found in poxviruses other than MCV, they are present in several gammaherpesviruses (6,8,9). MC159 interacts with Fasassociated protein with death domain (FADD) and procaspase-8 (formerly known as FADD-like interleukin-1␤-converting enzyme [FLICE]) and prevents Fas-and tumor necrosis factor alpha (TNF-␣)-induced apoptosis (6,(8)(9)(10). However, if caspase-8 is inhibited, receptor interacting protein kinase 1 (RIP1, RIPK1) is not cleaved and recruits RIP3 (RIPK3), initiating a pathway lead-

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…For all other immunoblot analyses, cells were lysed in boiling SDS-PAGE sample buffer. Immunofluorescence staining and detection were done as described previously (33).…”

Section: Methodsmentioning

confidence: 99%

Section: Characterization Of MCMV Mc159 Substitution Mutantsmentioning

confidence: 99%

mentioning

confidence: 99%

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Functional Comparison of Molluscum Contagiosum Virus vFLIP MC159 with Murine Cytomegalovirus M36/vICA and M45/vIRA Proteins

Hüttmann

Krause

Schommartz

et al. 2016

J Virol

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Programmed Necrosis in Host Defense

Mocarski

2023

Current Topics in Microbiology and Immunology

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Cytomegalovirus immune evasion of myeloid lineage cells

Brinkmann

Dağ

Hengel

et al. 2015

Med Microbiol Immunol

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Cytomegalovirus (CMV) evades the immune system in many different ways, allowing the virus to grow and its progeny to spread in the face of an adverse environment. Mounting evidence about the antiviral role of myeloid immune cells has prompted the research of CMV immune evasion mechanisms targeting these cells. Several cells of the myeloid lineage, such as monocytes, dendritic cells and macrophages, play a role in viral control, but are also permissive for CMV and are naturally infected by it. Therefore, CMV evasion of myeloid cells involves mechanisms that qualitatively differ from the evasion of non-CMV-permissive immune cells of the lymphoid lineage. The evasion of myeloid cells includes effects in cis, where the virus modulates the immune signaling pathways within the infected myeloid cell, and those in trans, where the virus affects somatic cells targeted by cytokines released from myeloid cells. This review presents an overview of CMV strategies to modulate and evade the antiviral activity of myeloid cells in cis and in trans.

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Murine Cytomegalovirus Virion-Associated Protein M45 Mediates Rapid NF-κB Activation after Infection

Cited by 28 publications

References 61 publications

Functional Comparison of Molluscum Contagiosum Virus vFLIP MC159 with Murine Cytomegalovirus M36/vICA and M45/vIRA Proteins

Functional Comparison of Molluscum Contagiosum Virus vFLIP MC159 with Murine Cytomegalovirus M36/vICA and M45/vIRA Proteins

Programmed Necrosis in Host Defense

Cytomegalovirus immune evasion of myeloid lineage cells

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