Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells.

Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, one B-box motif, one coiled-coil domain at the N-terminal, as well as one PRY domain and one SPRY domain at the C-terminal. TRIM21 is expressed in many tissues and plays an important role in systemic autoimmunity. However, TRIM21 plays different roles in different virus infections. In this study, we evaluate the relationship between porcine TRIM21 and PCV2 infection as well as host immune responses. We found that PCV2 infection modulated the expression of porcine TRIM21. TRIM21 can enhance interferons and proinflammatory factors and decrease cellular apoptosis in PCV2-infected cells. These results indicate that porcine TRIM21 plays a critical role in enhancing PCV2 infection, which is a promising target for controlling and developing the treatment of PCV2 infection.

Substrate recognition by TRIM and TRIM-like proteins in innate immunity.

TRIM (Tripartite motif) and TRIM-like proteins have emerged as an important class of E3 ligases in innate immunity. Their functions range from activation or regulation of innate immune signaling pathway to direct detection and restriction of pathogens. Despite the importance, molecular mechanisms for many TRIM/TRIM-like proteins remain poorly characterized, in part due to challenges of identifying their substrates. In this review, we discuss several TRIM/TRIM-like proteins in RNA sensing pathways and viral restriction functions. We focus on those containing PRY-SPRY, the domain most frequently used for substrate recognition, and discuss emerging mechanisms that are commonly utilized by several TRIM/TRIM-like proteins to tightly control their interaction with the substrates.

Gene expression profiling of the TRIM protein family reveals potential biomarkers for indicating tuberculosis status.

Tripartite motif (TRIM) family proteins play important regulatory roles in innate immune responses, the dysregulation of which cause several infectious diseases. However, the role and function of TRIM family proteins during tuberculosis (TB) infection remains unclear. In this study, we employed real-time quantitative PCR to profile the transcript levels of 72 TRIM genes from a cohort of 5 active TB patients, 5 latent tuberculosis infection (LTBI) subjects, and 5 healthy controls (HCs) in an initial discovery phase. The notable TRIM genes were assessed by in vitro cell infection experiments and further validated in another independent cohort (36 active TB, 24 LTBI and 28 HCs). The receiver operating characteristic (ROC) was used to analyze the diagnostic power of these TRIM genes. Our results revealed that 20 TRIM genes were decreased in active TB compared to LTBI and HCs. In addition, TRIM4, 16, 27, 32, 35, 46, 47, 65 and 68 were further shown to be downregulated in Mycobacterium smegmatis-infected macrophages and were found to be closely correlated with infection time and initial bacteria loads. Furthermore, the ROC analyses showed that TRIM4, 27 and 65 all exhibited the highest areas under the curve (AUC) values of 1.00 in discriminating active TB from LTBI and HCs. Moreover, TRIM27 combined with TRIM32 for an improved AUC value of 0.81 in discriminating LTBI from HCs. These results suggest that TRIM gene dysregulation might be involved in the pathogenesis of TB and that these genes could serve as potential biomarkers for indicating TB status.