ECTV Abolishes the Ability of GM-BM Cells to Stimulate Allogeneic CD4 T Cells in a Mouse Strain-Independent Manner

Szulc-Dąbrowska, Lidia; Wojtyniak, Piotr; Struzik, Justyna; Toka, Felix N.; Winnicka, A.; Gieryńska, Małgorzata

doi:10.1080/08820139.2019.1569676

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…ECTV is the causative agent of murinepox, an acute systemic disease with high mortality in susceptible strains of mice, and this virus is used as a model to study orthopoxvirus infection [21,22]. Mousepox has been a serious threat to laboratory mouse colonies in the past [7,23,24].…”

Section: Discussionmentioning

confidence: 99%

The Establishment of a Recombinant Polymerase Amplification Technique for the Detection of Mouse Poxvirus

Lian

Zhang

Zhu

et al. 2023

Preprint

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Background: Ectromelia virus (ECTV) is the pathogen of mousepox, which has a limited host range and a high mortality rate. In the past century, ECTV has affected laboratory mouse colonies worldwide. Recombinant polymerase amplification (RPA), which is widely used in virus detection, is an isothermal amplification method. Results: In this study, a probe-based RPA detection method was established for rapid and sensitive detection of ECTV.Primers were designed for the highly conserved region of crmD gene, the main core protein of recessive poxvirus, and standard plasmids were constructed.The sensitivity of the RPA assay is 100 copies of the genome per reaction. In addition, the method showed high specificity and did not cross-react with other common mouse viruses.Therefore, the practicability of the RPA method in the field was confirmed by the detection of 52 clinical samples. The real-time RPA assay was very similar to the ECTV real-time PCR assay, with 100% agreement. Conclusions: In conclusion, this RPA assay, especially in low-resource settings, provides a novel alternative for sensitive, simple, and specific identification of ECTV.

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Section: Discussionmentioning

confidence: 99%

The Establishment of a Recombinant Polymerase Amplification Technique for the Detection of Mouse Poxvirus

Lian

Zhang

Zhu

et al. 2023

Preprint

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“…Both ECTV and C15 specifically have been previously implicated in interference with CD4 + T cell function, however without elucidation of underlying mechanism. ECTV has been suggested to interfere with dendritic cell activation, though the responsible viral factor was not identified [ 72 , 73 ]. A previous publication described C15 as a virulence factor that targets both CD4 + and CD8 + T cells [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Ectromelia-encoded virulence factor C15 specifically inhibits antigen presentation to CD4+ T cells post peptide loading

et al. 2020

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Smallpox and monkeypox pose severe threats to human health. Other orthopoxviruses are comparably virulent in their natural hosts, including ectromelia, the cause of mousepox. Disease severity is linked to an array of immunomodulatory proteins including the B22 family, which has homologs in all pathogenic orthopoxviruses but not attenuated vaccine strains. We demonstrate that the ectromelia B22 member, C15, is necessary and sufficient for selective inhibition of CD4 + but not CD8 + T cell activation by immunogenic peptide and superantigen. Inhibition is achieved not by down-regulation of surface MHC- II or co-stimulatory protein surface expression but rather by interference with antigen presentation. The appreciable outcome is interference with CD4 + T cell synapse formation as determined by imaging studies and lipid raft disruption. Consequently, CD4 + T cell activating stimulus shifts to uninfected antigen-presenting cells that have received antigen from infected cells. This work provides insight into the immunomodulatory strategies of orthopoxviruses by elucidating a mechanism for specific targeting of CD4 + T cell activation, reflecting the importance of this cell type in control of the virus.

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“…Moreover, VACV-induced apoptosis in those cell populations, in contrast to the B cell line, indicated that VACV can differently affect various antigen presenting cells. These data demonstrate that the impairment of antigen presenting cells’ critical functions is the OPXVs pathway for the evasion of innate immune protective mechanisms [ 144 , 147 ]. In addition, mice lacking the components of the complement system developed severe mousepox with increased mortality when challenged with ECTV [ 148 ].…”

Section: Stimulation Of the Protective Immune Response—long Memory Ag...mentioning

confidence: 99%

“…Furthermore, an in vitro challenge of JAW II DCs and RAW 264.7 macrophage cell lines with ECTV revealed that the virus affected the downstream pathway dependent on non-canonical NF-κB signaling, which is accountable, among others, for the stimulation of antiviral immunity. These data may suggest the impairment of the development of adaptive immunity in the first stages of ECTV infection [ 144 , 145 , 146 ]. These results are in accordance with data obtained by Rhem et al from the VACV model, indicating the ability of the virus to modulate the first steps of adaptive immune response induction.…”

Section: Stimulation Of the Protective Immune Response—long Memory Ag...mentioning

confidence: 99%

Orthopoxvirus Zoonoses—Do We Still Remember and Are Ready to Fight?

et al. 2023

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The eradication of smallpox was an enormous achievement due to the global vaccination program launched by World Health Organization. The cessation of the vaccination program led to steadily declining herd immunity against smallpox, causing a health emergency of global concern. The smallpox vaccines induced strong, humoral, and cell-mediated immune responses, protecting for decades after immunization, not only against smallpox but also against other zoonotic orthopoxviruses that now represent a significant threat to public health. Here we review the major aspects regarding orthopoxviruses’ zoonotic infections, factors responsible for viral transmissions, as well as the emerging problem of the increased number of monkeypox cases recently reported. The development of prophylactic measures against poxvirus infections, especially the current threat caused by the monkeypox virus, requires a profound understanding of poxvirus immunobiology. The utilization of animal and cell line models has provided good insight into host antiviral defenses as well as orthopoxvirus evasion mechanisms. To survive within a host, orthopoxviruses encode a large number of proteins that subvert inflammatory and immune pathways. The circumvention of viral evasion strategies and the enhancement of major host defenses are key in designing novel, safer vaccines, and should become the targets of antiviral therapies in treating poxvirus infections.

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ECTV Abolishes the Ability of GM-BM Cells to Stimulate Allogeneic CD4 T Cells in a Mouse Strain-Independent Manner

Cited by 6 publications

References 57 publications

The Establishment of a Recombinant Polymerase Amplification Technique for the Detection of Mouse Poxvirus

The Establishment of a Recombinant Polymerase Amplification Technique for the Detection of Mouse Poxvirus

Ectromelia-encoded virulence factor C15 specifically inhibits antigen presentation to CD4+ T cells post peptide loading

Orthopoxvirus Zoonoses—Do We Still Remember and Are Ready to Fight?

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