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Pregled bibliografske jedinice broj: 1105791

Mouse cytomegalovirus m153 protein stabilizes expression of the inhibitory NKR-P1B ligand, Clr-b.


Aguilar, OA; Sampaio, IS; Rahim, MMA; Samaniego, JD; Tilahun, M; , Krishnamoorthy, M; Popović, B; Babić, M; Krmpotić, A; Treanor, B et al.
Mouse cytomegalovirus m153 protein stabilizes expression of the inhibitory NKR-P1B ligand, Clr-b. // Journal of Virology, 94 (2019), 1; 01220-19 doi:10.1128/JVI.01220-19 (međunarodna recenzija, članak, znanstveni)


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Naslov
Mouse cytomegalovirus m153 protein stabilizes expression of the inhibitory NKR-P1B ligand, Clr-b.

Autori
Aguilar, OA ; Sampaio, IS ; Rahim, MMA ; Samaniego, JD ; Tilahun, M ; , Krishnamoorthy, M ; Popović, B ; Babić, M ; Krmpotić, A ; Treanor, B ; Margulies, DH ; Allan, DSJ ; Makrigiannis, AP ; Jonjić, S ; Carlyle, JR

Izvornik
Journal of Virology (0022-538X) 94 (2019), 1; 01220-19

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
MCMV ; Nkrp1-Clr ; host-pathogen interactions ; m145 family ; missing-self recognition ; mouse cytomegalovirus ; natural killer cell ; natural killer cells ; viral immune evasion.

Sažetak
Natural killer (NK) cells are a subset of innate lymphoid cells (ILC) capable of recognizing stressed and infected cells through multiple germ line-encoded receptor-ligand interactions. Missing-self recognition involves NK cell sensing of the loss of host-encoded inhibitory ligands on target cells, including MHC class I (MHC-I) molecules and other MHC-I- independent ligands. Mouse cytomegalovirus (MCMV) infection promotes a rapid host-mediated loss of the inhibitory NKR-P1B ligand Clr-b (encoded by Clec2d) on infected cells. Here we provide evidence that an MCMV m145 family member, m153, functions to stabilize cell surface Clr-b during MCMV infection. Ectopic expression of m153 in fibroblasts augments Clr- b cell surface levels. Moreover, infections using m153-deficient MCMV mutants (Δm144-m158 and Δm153) show an accelerated and exacerbated Clr-b downregulation. Importantly, enhanced loss of Clr-b during Δm153 mutant infection reverts to wild-type levels upon exogenous m153 complementation in fibroblasts. While the effects of m153 on Clr-b levels are independent of Clec2d transcription, imaging experiments revealed that the m153 and Clr-b proteins only minimally colocalize within the same subcellular compartments, and tagged versions of the proteins were refractory to coimmunoprecipitation under mild-detergent conditions. Surprisingly, the Δm153 mutant possesses enhanced virulence in vivo, independent of both Clr-b and NKR-P1B, suggesting that m153 potentially targets additional host factors. Nevertheless, the present data highlight a unique mechanism by which MCMV modulates NK ligand expression.IMPORTANCE Cytomegaloviruses are betaherpesviruses that in immunocompromised individuals can lead to severe pathologies. These viruses encode various gene products that serve to evade innate immune recognition. NK cells are among the first immune cells that respond to CMV infection and use germ line- encoded NK cell receptors (NKR) to distinguish healthy from virus-infected cells. One such axis that plays a critical role in NK recognition involves the inhibitory NKR-P1B receptor, which engages the host ligand Clr-b, a molecule commonly lost on stressed cells ("missing-self"). In this study, we discovered that mouse CMV utilizes the m153 glycoprotein to circumvent host-mediated Clr-b downregulation, in order to evade NK recognition. These results highlight a novel MCMV-mediated immune evasion strategy.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Ustanove:
Medicinski fakultet, Rijeka

Poveznice na cjeloviti tekst rada:

doi

Citiraj ovu publikaciju:

Aguilar, OA; Sampaio, IS; Rahim, MMA; Samaniego, JD; Tilahun, M; , Krishnamoorthy, M; Popović, B; Babić, M; Krmpotić, A; Treanor, B et al.
Mouse cytomegalovirus m153 protein stabilizes expression of the inhibitory NKR-P1B ligand, Clr-b. // Journal of Virology, 94 (2019), 1; 01220-19 doi:10.1128/JVI.01220-19 (međunarodna recenzija, članak, znanstveni)
Aguilar, O., Sampaio, I., Rahim, M., Samaniego, J., Tilahun, M., , Krishnamoorthy, M, Popović, B., Babić, M., Krmpotić, A. & Treanor, B. (2019) Mouse cytomegalovirus m153 protein stabilizes expression of the inhibitory NKR-P1B ligand, Clr-b.. Journal of Virology, 94 (1), 01220-19 doi:10.1128/JVI.01220-19.
@article{article, author = {Aguilar, OA and Sampaio, IS and Rahim, MMA and Samaniego, JD and Tilahun, M and Popovi\'{c}, B and Babi\'{c}, M and Krmpoti\'{c}, A and Treanor, B and Margulies, DH and Allan, DSJ and Makrigiannis, AP and Jonji\'{c}, S and Carlyle, JR}, year = {2019}, pages = {01220-19-01220-19}, DOI = {10.1128/JVI.01220-19}, keywords = {MCMV, Nkrp1-Clr, host-pathogen interactions, m145 family, missing-self recognition, mouse cytomegalovirus, natural killer cell, natural killer cells, viral immune evasion.}, journal = {Journal of Virology}, doi = {10.1128/JVI.01220-19}, volume = {94}, number = {1}, issn = {0022-538X}, title = {Mouse cytomegalovirus m153 protein stabilizes expression of the inhibitory NKR-P1B ligand, Clr-b.}, keyword = {MCMV, Nkrp1-Clr, host-pathogen interactions, m145 family, missing-self recognition, mouse cytomegalovirus, natural killer cell, natural killer cells, viral immune evasion.} }
@article{article, author = {Aguilar, OA and Sampaio, IS and Rahim, MMA and Samaniego, JD and Tilahun, M and Popovi\'{c}, B and Babi\'{c}, M and Krmpoti\'{c}, A and Treanor, B and Margulies, DH and Allan, DSJ and Makrigiannis, AP and Jonji\'{c}, S and Carlyle, JR}, year = {2019}, pages = {01220-19-01220-19}, DOI = {10.1128/JVI.01220-19}, keywords = {MCMV, Nkrp1-Clr, host-pathogen interactions, m145 family, missing-self recognition, mouse cytomegalovirus, natural killer cell, natural killer cells, viral immune evasion.}, journal = {Journal of Virology}, doi = {10.1128/JVI.01220-19}, volume = {94}, number = {1}, issn = {0022-538X}, title = {Mouse cytomegalovirus m153 protein stabilizes expression of the inhibitory NKR-P1B ligand, Clr-b.}, keyword = {MCMV, Nkrp1-Clr, host-pathogen interactions, m145 family, missing-self recognition, mouse cytomegalovirus, natural killer cell, natural killer cells, viral immune evasion.} }

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