Poxviruses and the Immune System: Implications for Monkeypox Virus

Overview

Journal Int Immunopharmacol

Specialties Allergy & Immunology
Pharmacology

Date 2022 Oct 25

PMID 36283221

Authors

Amene Saghazadeh

Nima Rezaei

Affiliations

Soon will be listed here.

Abstract

Poxviruses (PXVs) are mostly known for the variola virus, being the cause of smallpox; however, re-emerging PXVs have also shown a great capacity to develop outbreaks of pox-like infections in humans. The situation is alarming; PXV outbreaks have been involving both endemic and non-endemic areas in recent decades. Stopped smallpox vaccination is a reason offered mainly for this changing epidemiology that implies the protective role of immunity in the pathology of PXV infections. The immune system recognizes PXVs and elicits responses, but PXVs can antagonize these responses. Here, we briefly review the immunology of PXV infections, with emphasis on the role of pattern-recognition receptors, macrophages, and natural killer cells in the early response to PXV infections and PXVs' strategies influencing these responses, as well as taking a glance at other immune cells, which discussion over them mainly occurs in association with PXV immunization rather than PXV infection. Throughout the review, numerous evasion mechanisms are highlighted, which might have implications for designing specific immunotherapies for PXV in the future.

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References

Martinez O, Miranda E, Ramirez M, Santos S, Rivera C, Vazquez L . Immunomodulator-based enhancement of anti smallpox immune responses. PLoS One. 2015; 10(4):e0123113. PMC: 4395221. DOI: 10.1371/journal.pone.0123113. View

Hazlewood J, Dumenil T, Le T, Slonchak A, Kazakoff S, Patch A . Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures. PLoS Pathog. 2021; 17(1):e1009215. PMC: 7837487. DOI: 10.1371/journal.ppat.1009215. View

Nathan C . Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006; 6(3):173-82. DOI: 10.1038/nri1785. View

Stutte S, Ruf J, Kugler I, Ishikawa-Ankerhold H, Parzefall A, Marconi P . Type I interferon mediated induction of somatostatin leads to suppression of ghrelin and appetite thereby promoting viral immunity in mice. Brain Behav Immun. 2021; 95:429-443. DOI: 10.1016/j.bbi.2021.04.018. View

Altenburg A, van de Sandt C, Li B, MacLoughlin R, Fouchier R, van Amerongen G . Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo. Sci Rep. 2017; 7(1):8580. PMC: 5561217. DOI: 10.1038/s41598-017-08719-y. View

Song H, Josleyn N, Janosko K, Skinner J, Reeves R, Cohen M . Monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions. PLoS One. 2013; 8(10):e77804. PMC: 3798392. DOI: 10.1371/journal.pone.0077804. View

Scutts S, Ember S, Ren H, Ye C, Lovejoy C, Mazzon M . DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing. Cell Rep. 2018; 25(7):1953-1965.e4. PMC: 6250978. DOI: 10.1016/j.celrep.2018.10.034. View

Beauchamp N, Busick R, Alexander-Miller M . Functional divergence among CD103+ dendritic cell subpopulations following pulmonary poxvirus infection. J Virol. 2010; 84(19):10191-9. PMC: 2937786. DOI: 10.1128/JVI.00892-10. View

Zavala F, Rodrigues M, Rodriguez D, Rodriguez J, Nussenzweig R, Esteban M . A striking property of recombinant poxviruses: efficient inducers of in vivo expansion of primed CD8(+) T cells. Virology. 2001; 280(2):155-9. DOI: 10.1006/viro.2000.0792. View

10.

Ferguson B, Mansur D, Peters N, Ren H, Smith G . DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. Elife. 2012; 1:e00047. PMC: 3524801. DOI: 10.7554/eLife.00047. View

11.

Forster R, Wolf G, Mayr A . Highly attenuated poxviruses induce functional priming of neutrophils in vitro. Arch Virol. 1994; 136(1-2):219-26. DOI: 10.1007/BF01538831. View

12.

Xu R, Wong E, Rubio D, Roscoe F, Ma X, Nair S . Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection. Immunity. 2015; 43(6):1148-59. PMC: 4684903. DOI: 10.1016/j.immuni.2015.11.015. View

13.

Sharp D, Lattime E . Recombinant Poxvirus and the Tumor Microenvironment: Oncolysis, Immune Regulation and Immunization. Biomedicines. 2017; 4(3). PMC: 5298125. DOI: 10.3390/biomedicines4030019. View

14.

Wang F, Gao X, Barrett J, Shao Q, Bartee E, Mohamed M . RIG-I mediates the co-induction of tumor necrosis factor and type I interferon elicited by myxoma virus in primary human macrophages. PLoS Pathog. 2008; 4(7):e1000099. PMC: 2438611. DOI: 10.1371/journal.ppat.1000099. View

15.

Baldanta S, Fernandez-Escobar M, Acin-Perez R, Albert M, Camafeita E, Jorge I . ISG15 governs mitochondrial function in macrophages following vaccinia virus infection. PLoS Pathog. 2017; 13(10):e1006651. PMC: 5659798. DOI: 10.1371/journal.ppat.1006651. View

16.

Garcia-Arriaza J, Gomez C, Sorzano C, Esteban M . Deletion of the vaccinia virus N2L gene encoding an inhibitor of IRF3 improves the immunogenicity of modified vaccinia virus Ankara expressing HIV-1 antigens. J Virol. 2014; 88(6):3392-410. PMC: 3957918. DOI: 10.1128/JVI.02723-13. View

17.

Hatfield S, Daniels K, ODonnell C, Waggoner S, Welsh R . Weak vaccinia virus-induced NK cell regulation of CD4 T cells is associated with reduced NK cell differentiation and cytolytic activity. Virology. 2018; 519:131-144. PMC: 5971155. DOI: 10.1016/j.virol.2018.04.012. View

18.

Perkins D, Polumuri S, Pennini M, Lai W, Xie P, Vogel S . Reprogramming of murine macrophages through TLR2 confers viral resistance via TRAF3-mediated, enhanced interferon production. PLoS Pathog. 2013; 9(7):e1003479. PMC: 3708851. DOI: 10.1371/journal.ppat.1003479. View

19.

Meade N, Furey C, Li H, Verma R, Chai Q, Rollins M . Poxviruses Evade Cytosolic Sensing through Disruption of an mTORC1-mTORC2 Regulatory Circuit. Cell. 2018; 174(5):1143-1157.e17. PMC: 6172959. DOI: 10.1016/j.cell.2018.06.053. View

20.

Marq J, Hausmann S, Luban J, Kolakofsky D, Garcin D . The double-stranded RNA binding domain of the vaccinia virus E3L protein inhibits both RNA- and DNA-induced activation of interferon beta. J Biol Chem. 2009; 284(38):25471-8. PMC: 2757948. DOI: 10.1074/jbc.M109.018895. View