Structural properties of a viral orthologue of cellular CD200 protein: KSHV vOX2

Amini, Abbas; Solovyova, Alexandra S.; Sadeghian, Hamid; Blackbourn, David J.; Rezaee, Seyed Abdolrahim

doi:10.1016/j.virol.2014.10.020

Cited by 5 publications

(1 citation statement)

References 60 publications

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“…The reason for this is not known, but the presence of specific T‐cell responses suggests that expression of the U85 protein and generation of the CD4 T‐cell epitope also occurs during natural infections. U85 is a predicted membrane glycoprotein homolog of the human OX2 or CD200 , a widely distributed glycoprotein that exerts a variety of immunomodulatory effects by interacting with its receptor CD200R, which is expressed on lymphoid and myeloid cells . CD200 homologs have been described for other viruses including herpesviruses HHV‐7 and HHV‐8 .…”

Section: Discussionmentioning

confidence: 99%

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

et al. 2019

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Human herpes virus 6B (HHV‐6B) is a widespread virus that infects most people early in infancy and establishes a chronic life‐long infection with periodic reactivation. CD4 T cells have been implicated in control of HHV‐6B, but antigenic targets and functional characteristics of the CD4 T‐cell response are poorly understood. We identified 25 naturally processed MHC‐II peptides, derived from six different HHV‐6B proteins, and showed that they were recognized by CD4 T‐cell responses in HLA‐matched donors. The peptides were identified by mass spectrometry after elution from HLA‐DR molecules isolated from HHV‐6B‐infected T cells. The peptides showed strong binding to matched HLA alleles and elicited recall T‐cell responses in vitro. T‐cell lines expanded in vitro were used for functional characterization of the response. Responding cells were mainly CD3+CD4+, produced IFN‐γ, TNF‐α, and low levels of IL‐2, alone or in combination, highlighting the presence of polyfunctional T cells in the overall response. Many of the responding cells mobilized CD107a, stored granzyme B, and mediated specific killing of peptide‐pulsed target cells. These results highlight a potential role for polyfunctional cytotoxic CD4 T cells in the long‐term control of HHV‐6B infection.

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Section: Discussionmentioning

confidence: 99%

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

et al. 2019

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Protein homodimer sequestration with small molecules: Focus on PD-L1

Bailly

Vergoten

2020

Biochemical Pharmacology

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Membrane-Associated and Secreted Forms of the Rhesus Macaque Rhadinovirus-Encoded CD200 Homologue and Cellular CD200 Demonstrate Differential Effects on Rhesus Macaque CD200 Receptor Signaling and Regulation of Myeloid Cell Activation

Estep

Govindan

Fitzpatrick

et al. 2021

J Virol

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The CD200-CD200R pathway is involved in inhibition of immune responses, and the importance of this pathway to infectious disease is highlighted by the fact that viral CD200 (vCD200) molecules have been found to be encoded by several DNA viruses, including the human gammaherpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV), and the closely related rhesus macaque rhadinovirus (RRV). KSHV vCD200 is the most extensively studied vCD200 molecule, however, the only herpesvirus vCD200 molecule to be examined in vivo is that encoded by RRV. Our prior studies have demonstrated that RRV vCD200 is a functional CD200 homologue that is capable of affecting immune responses in vivo, and further, that RRV can express a secreted form of vCD200 (vCD200-Sec) during infection. Despite this information, RRV vCD200 has not been examined specifically for effects on RM CD200R signaling, and the functionality of vCD200-Sec has not been examined in any context. Thus, we developed an in vitro model system in which B cells expressing vCD200 were utilized to assess the effects of this molecule on the regulation of myeloid cells expressing RM CD200R, mimicking interactions that are predicted to occur in vivo. Our findings suggest that RRV vCD200 can bind and induce functional signals through RM CD200R, while vCD200-Sec represents a non-functional protein incapable of affecting CD200R signaling. We also provide the first demonstration of the function of RM CD200, which appears to possess more robust signaling capabilities than RRV vCD200, and also show that KSHV vCD200 does not efficiently induce signaling via RM CD200R.IMPORTANCE Viral CD200 homologues are encoded by KSHV and the closely related RRV. Though RRV vCD200 has been examined, questions still exist in regard to the ability of this molecule to induce signaling via rhesus macaque CD200R, as well as the potential function of a secreted form of vCD200. Further, all previous in vitro studies of RRV vCD200 have utilized an Fc fusion protein to examine functionality, which does not replicate the structural properties of the membrane-associated form of vCD200 that is naturally produced during RRV infection. In this study, we demonstrate for the first time that membrane-expressed RRV vCD200 is capable of inducing signal transduction via RM CD200R, while the secreted form of vCD200 appears to be non-functional. Further, we also demonstrate that RM CD200 induces signaling via RM CD200R, and is more robust than RRV vCD200, while KSHV vCD200 does not appear to induce efficient signaling via RM CD200R.

show abstract

Structural properties of a viral orthologue of cellular CD200 protein: KSHV vOX2

Cited by 5 publications

References 60 publications

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

Naturally processed HLA‐DR3‐restricted HHV‐6B peptides are recognized broadly with polyfunctional and cytotoxic CD4 T‐cell responses

Protein homodimer sequestration with small molecules: Focus on PD-L1

Membrane-Associated and Secreted Forms of the Rhesus Macaque Rhadinovirus-Encoded CD200 Homologue and Cellular CD200 Demonstrate Differential Effects on Rhesus Macaque CD200 Receptor Signaling and Regulation of Myeloid Cell Activation

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