Viral CD229 (Ly9) homologs as new manipulators of host immunity

Abstract

The signaling lymphocytic activation molecule family (SLAMF) of receptors plays crucial roles during innate and adaptive immune responses. The SLAMF member CD229 (Ly9, SLAMF3) is a homophilic receptor predominantly expressed on the surface of B and T cells. CD229 acts as a cosignaling molecule, regulating lymphocyte homoeostasis and activation. To promote viral replication and survival in their hosts, viruses have developed sophisticated mechanisms to combat and avoid immune surveillance. Many of these strategies rely on host defense genes captured during the process of virus–host coevolution. In particular, large DNA viruses devote a wide range of proteins to interfere with almost every host immune pathway. Given that CD229 is critically involved in regulating immune responses, it is not surprising that viruses have designed tactics to mimic or interfere with this receptor. The discovery, in recent years, that some viruses have hijacked CD229 genes from their hosts, incorporating them as an integral part of their genomes, or have evolved proteins to directly target CD229, indicates that this is the case. While it is still an emerging area of research, the present review discusses these viral molecules and their potential in immune modulation. A more detailed understanding of the mechanisms of action and the functional implications of these new viral CD229 mimics may not only provide seminal information on viral immune evasion mechanisms but also, unveil unrecognized aspects of CD229 immune functions.

Identification of Autophagy- and Ferroptosis-Related lncRNAs Functioned through Immune-Related Pathways in Head and Neck Squamous Carcinoma

“…Among these, PLAC8 were found to regulate autophagy-related functions in a variety of cancers [ 51 , 52 ]. In addition, numerous DEGs were reported to be involved in the proliferation and differentiation of immune cells and could regulate immune functions, including CD226 , IRF4 , LY9 , MS4A1 , TBX21 , TNFRSF17 , FCRLA , and SLAMF6 [ 45 , 53 , 54 , 55 , 56 , 57 , 58 ].…”

“…For example, PCED1B-AS1 could inhibit tumor cell death by cooperating with the miR-194-5p/PCED1B axis in glioma [ 93 ], and MIR4435-2HG could regulate cancer proliferation through sponging miR-206 , miR-802 , miR-128-3 and miR-1224-5p and regulated YAP1 , FLOT2 , et al, in various cancers [ 73 , 94 , 95 , 96 ]. Among all these DEGs, nearly half (24/56) have been reported to be involved in activation and differentiation of immune cells or regulation of the immune response [ 45 , 53 , 54 , 55 , 56 , 57 , 58 ]. One of them, placenta associated 8 ( PLAC8 ), has been reported to regulate autophagy by suppressing the production of IL-18, which is a pro-inflammatory cytokine that is capable of stimulating interferon gamma production and of regulating T helper cell responses [ 97 ].…”

“…Life 2021, 11, x FOR PEER REVIEW 9 of 18 in a variety of cancers [51,52]. In addition, numerous DEGs were reported to be involved in the proliferation and differentiation of immune cells and could regulate immune functions, including CD226, IRF4, LY9, MS4A1, TBX21, TNFRSF17, FCRLA, and SLAMF6 [45,[53][54][55][56][57][58]. To further characterize and understand the biological insights of these DEGs, we performed gene ontology (GO) and KEGG analysis.…”

Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma

“…Among these regulators, BZW1 is a transcription factor related to the regulation of cell cycle and proliferation [ 30 ]. LY9 was a member of SLAM family of immunomodulatory receptors [ 31 ] and interacted with the adaptor molecule signaling lymphocyte activation molecule-associated proteins. A previous study showed LY9 was related to the cancer progression and correlated to overall survival of the patients with breast cancer.…”

SLAMF8, a potential novel immune checkpoint molecule, is associated with the prognosis of colorectal cancer

“…The signaling lymphocytic activation molecule (SLAM) family is a member of the CD2 protein family and is differentially expressed on the surface of immune cells 10 . Recent studies have indicated that signaling lymphocytic activation molecule family member (SLAMF) is involved in regulating adaptive and innate immune responses [11][12][13] . SLAMF7 signaling reprograms T cells toward exhaustion in the tumor microenvironment [14][15][16] .…”