Tripartite Motif Family Research Articles

Porcine TRIM21 RING-finger E3 ubiquitin ligase is essential for anti-PRRSV activity

Porcine reproductive and respiratory syndrome (PRRS) causes substantial economic losses to the global pig industry. Members of the tripartite motif (TRIM) family are the important effectors of the innate immune response against viral infections. We have previously characterized the entire porcine TRIM (pTRIM) family, and predicted pTRIM5, 14, 21, 25 and 38 as host restriction factors against PRRSV infection. However, little is known about whether and how pTRIMs restrict the infection of PRRSV. In this study, we firstly performed the amino acid alignments of the RING domain of pTRIM5, 21, 25 and 38, and found that pTRIM proteins contained the characteristic consensus C3HC4 type zinc-binding motif which is important for the ubiquitination function. Then we detected the mRNA changes of pTRIMs in porcine alveolar macrophages (PAMs) by transcriptome sequencing after PRRSV infection in piglets. Transcriptional profiles showed that the expression of pTRIM5, 21 and 26 was significantly (P < 0.05) up-regulated, consistent with their expression in vitro. Finally, as the most up-regulated gene after PRRSV infection both in vivo and in vitro, pTRIM21 was investigated for its anti-PRRSV activity in immortalized PAMs (iPAMs) in two aspects: knockdown and overexpression of pTRIM21. Knockdown of endogenic pTRIM21 could significantly promote PRRSV replication at 12 and 24 h post infection in iPAMs. Meanwhile, overexpression of pTRIM21 could significantly suppress PRRSV replication but not affect its attachment and endocytosis. Moreover, pTRIM21 RING-finger E3 ubiquitin ligase was essential for anti-PRRSV activity. Our data enhance our understanding of the pTRIMs against PRRSV infection, which may help us develop novel therapeutic tools to control PRRSV.

Inhibition of TRIM14 protects cerebral ischemia/reperfusion injury through regulating NF-κB/NLRP3 pathway-mediated inflammation and apoptosis

Purpose Many proteins in tripartite motif (TRIM) family have been reported to play an important role in cerebral ischemia/reperfusion (I/R) injury. This study was designed to investigate the effect of TRIM14 on the cerebral I/R injury in rats. Methods The rat model was constructed through inserting thread into the middle cerebral artery. The expression of TRIM14 was measured by qRT-PCR, immunoblotting, and immunofluorescence. The hippocampal sections were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to determine infarct volume and used for measuring the neurologic deficit score and brain water content. The H&E staining was used for immunohistochemical (IHC) staining. The number of apoptotic cells was measured by fluorescence microscopy. The levels of IL-6, IL-1β, and TNFα were detected by qRT-PCR and ELISA. The swimming speed, latency time, and number of platform crossings were measured by the water maze test. Results TRIM14 was significantly enhanced in rats with cerebral I/R injury compared to Sham rats, showing its highest level at 24 h after I/R. TRIM14 inhibition reduced ischemic brain injury, suppressed neuron apoptosis, suppressed inflammation, and improved cognitive dysfunction in rats with cerebral I/R injury. TRIM14 inhibition also suppressed the activation of NF-κB/NLRP3 pathway in rats with cerebral I/R injury. Conclusion In conclusion, the expression of TRIM14 was increased in rats with cerebral I/R injury, the protective effect of TRIM14 inhibitor on cerebral I/R injury in rats depends on its anti-apoptotic and anti-inflammatory effect. The underlying mechanism was, at least partially, through regulating NF-κB/NLRP3 pathway.

TRIM32: A Multifunctional Protein Involved in Muscle Homeostasis, Glucose Metabolism, and Tumorigenesis.

Human tripartite motif family of proteins 32 (TRIM32) is a ubiquitous multifunctional protein that has demonstrated roles in differentiation, muscle physiology and regeneration, and tumor suppression. Mutations in TRIM32 result in two clinically diverse diseases. A mutation in the B-box domain gives rise to Bardet–Biedl syndrome (BBS), a disease whose clinical presentation shares no muscle pathology, while mutations in the NHL (NCL-1, HT2A, LIN-41) repeats of TRIM32 causes limb-girdle muscular dystrophy type 2H (LGMD2H). TRIM32 also functions as a tumor suppressor, but paradoxically is overexpressed in certain types of cancer. Recent evidence supports a role for TRIM32 in glycolytic-mediated cell growth, thus providing a possible mechanism for TRIM32 in the accumulation of cellular biomass during regeneration and tumorigenesis, including in vitro and in vivo approaches, to understand the broad spectrum of TRIM32 functions. A special emphasis is placed on the utility of the Drosophila model, a unique system to study glycolysis and anabolic pathways that contribute to the growth and homeostasis of both normal and tumor tissues.

Full-length transcriptome sequencing and identification and immune response of TRIM genes in Dabry's sturgeon (Acipenser dabryanus)

Acipenser dabryanus, also called Yangtze sturgeon or Dabry's sturgeon, is an endemic species restricted to the upper reaches of the Yangtze River in China. In the present study, we conducted the first full-length transcriptome analysis of A. dabryanus by the use of SMRT sequencing technology. Transcriptome sequencing generated a total of 155,348 unigenes with a mean length of 2996 bp. A total of 131,711 (84.78%) unigenes were annotated in various databases and comparative analysis was performed between A. dabryanus and its the related species. Based on the sequence information, three members in the tripartite motif (TRIM) family, namely, TRIM32, TRIM36 and TRIM71, were identified. The full-length TRIM genes encoded polypeptides with a typical TRIM structure: a RING domain, one or two B-box domains, and variable domains at the C-terminus. Gene expression profile analysis showed that the three TRIM genes were constitutively expressed in A. dabryanus, and the highest expression levels of TRIM32 and TRIM36 were found in the brain, while TRIM71 was predominantly expressed in the muscle. Upon challenge with the bacterial pathogen Edwardsiella tarda, significant upregulation of TRIMs was observed in both mucosal and systemic-associated immune tissues. Our data revealed the possible functional role of TRIMs in both mucosal and systemic defence of A. dabryanus in the immune response against bacterial infection.

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense.

The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape strategies to subvert TRIM-mediated mechanisms. In this review, we focus on their regulation of IFN-I-mediated innate immune response, which plays key roles in antiviral and antitumor defense.

TRIM65 in White Matter Lesions, Innate Immunity, and Tumor.

Most of the tripartite motif (TRIM) family proteins have E3 ubiquitin ligase activities and also have a variety of functions in cellular processes such as intracellular signal transduction, apoptosis, innate immunity, and carcinogenesis. TRIM65 is a member of the TRIM family. More pieces of evidence have shown a unique role and importance of TRIM65 protein in the occurrence and development of some diseases. In this review, the importance of TRIM65 in white matter lesions, innate immunity, and the effect of tumors were mainly reviewed.

Tripartite Motif 22 (TRIM22) protein restricts herpes simplex virus 1 by epigenetic silencing of viral immediate-early genes.

Intrinsic resistance is a crucial line of defense against virus infections, and members of the Tripartite Ring Interaction Motif (TRIM) family of proteins are major players in this system, such as cytoplasmic TRIM5α or nuclear promyelocytic leukemia (PML/TRIM19) protein. Previous reports on the antiviral function of another TRIM protein, TRIM22, emphasized its innate immune role as a Type I and Type II interferon-stimulated gene against RNA viruses. This study shows that TRIM22 has an additional intrinsic role against DNA viruses. Here, we report that TRIM22 is a novel restriction factor of HSV-1 and limits ICP0-null virus replication by increasing histone occupancy and heterochromatin, thereby reducing immediate-early viral gene expression. The corresponding wild-type equivalent of the virus evades the TRIM22-specific restriction by a mechanism independent of ICP0-mediated degradation. We also demonstrate that TRIM22 inhibits other DNA viruses, including representative members of the β- and γ- herpesviruses. Allelic variants in TRIM22 showed different degrees of anti-herpesviral activity; thus, TRIM22 genetic variability may contribute to the varying susceptibility to HSV-1 infection in humans. Collectively, these results argue that TRIM22 is a novel restriction factor and expand the list of restriction factors functioning in the infected cell nucleus to counter DNA virus infection.

Activation mechanisms of inflammasomes by bacterial toxins.

Inflammasomes are cytosolic innate immune complexes, which assemble in mammalian cells in response to microbial components and endogenous danger signals. A major family of inflammasome activators is bacterial toxins. Inflammasome sensor proteins, such as the nucleotide-binding oligomerisation domain-like receptor (NLR) family members NLRP1b and NLRP3, and the tripartite motif family member Pyrin+ efflux triggered by pore-forming toxins or by other toxin-induced homeostasis-altering events such as lysosomal rupture. Pyrin senses perturbation of host cell functions induced by certain enzymatic toxins resulting in impairment of RhoA GTPase activity. Assembly of the inflammasome complex activates the cysteine protease caspase-1, leading to the proteolytic cleavage of the proinflammatory cytokines IL-1β and IL-18, and the pore-forming protein gasdermin D causing pyroptosis. In this review, we discuss the latest progress in our understanding on the activation mechanisms of inflammasome complexes by bacterial toxins and effector proteins and explore avenues for future research into the relationships between inflammasomes and bacterial toxins.

The testis-specifically expressed gene Trim69 is not essential for fertility in mice.

Protein ubiquitination is essential for diverse cellular functions including spermatogenesis. The tripartite motif (TRIM) family proteins, most of which have E3 ubiquitin ligase activity, are highly conserved in mammals. They are involved in important cellular processes such as embryonic development, immunity, and fertility. Our previous studies indicated that Trim69, a testis-specific expressed TRIM family gene, potentially participates in the spermatogenesis by mediating testicular cells apoptosis. In this study, we investigated the biological functions of Trim69 in male mice by established Trim69 knockout mice with CRISPR/Cas9 genomic editing technology. Here, we reported that the male Trim69 knockout mice had normal fertility. The adult knockout mice have shown that the appearance of testes, testis/body weight ratios, testicular histomorphology, and the number and quality of sperm were consistent with wild-type mice. These results indicated that the E3 ubiquitin ligase protein Trim69 was not essential for male mouse fertility, and it might be compensated by other TRIM family members such as Trim58 in Trim69-deficiency testis. This study would help to elucidate the functions of tripartite motif protein family and the regulation of spermatogenesis.

Crystal structure and mutational analysis of the human TRIM7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1

Tripartite motif (TRIM)7 is an E3 ubiquitin ligase that was first identified through its interaction with glycogenin-1 (GN1), the autoglucosyltransferase that initiates glycogen biosynthesis. A growing body of evidence indicates that TRIM7 plays an important role in cancer development, viral pathogenesis, and atherosclerosis and, thus, represents a potential therapeutic target. TRIM family proteins share a multidomain architecture with a conserved N-terminal TRIM and a variable C-terminal domain. Human TRIM7 contains the canonical TRIM motif and a B30.2 domain at the C terminus. To contribute to the understanding of the mechanism of action of TRIM7, we solved the X-ray crystal structure of its B30.2 domain (TRIM7B30.2) in two crystal forms at resolutions of 1.6 Å and 1.8 Å. TRIM7B30.2 exhibits the typical B30.2 domain fold, consisting of two antiparallel β-sheets of seven and six strands, arranged as a distorted β-sandwich. Furthermore, two long loops partially cover the concave face of the β-sandwich defined by the β-sheet of six strands, thus forming a positively charged cavity. We used sequence conservation and mutational analyses to provide evidence of a putative binding interface for GN1. These studies showed that Leu423, Ser499, and Cys501 of TRIM7B30.2 and the C-terminal 33 amino acids of GN1 are critical for this binding interaction. Molecular dynamics simulations also revealed that hydrogen bond and hydrophobic interactions play a major role in the stability of a modeled TRIM7B30.2-GN1 C-terminal peptide complex. These data provide useful information that could be used to target this interaction for the development of potential therapeutic agents.

TRIM52 knockdown inhibits cell proliferation and induces apoptosis through activation of the STAT3 pathway in ovarian cancer1

Ovarian cancer (OC) is a common gynecologic malignancy worldwide. Several members of the tripartite motif (TRIM) family are of great importance in various human malignancies. In this study, we aimed to figure out the function and mechanism of TRIM52 in OC. Western blot and RT–PCR were used to examine the expression level of TRIM52. Cell counting kit-8 (CCK-8) assay was used to measure cell proliferation. Annexin V/ PI kit and TUNEL assay were carried out to test cell apoptosis. Knockdown of TRIM52 significantly inhibited cell proliferation and induced cell apoptosis. Glucose uptake, lactate, and ATP production were depressed after TRIM52 silencing. Furthermore, loss of TRIM52 decreased the levels of pyruvate kinase isozyme M2, glucose transporter protein 1, and p-STAT3. Overexpression of TRIM52 showed effects that were opposite as those of TRIM52 knockdown; these effects were alleviated by AG490, which is an inhibitor of STAT3. In addition, TRIM52 knockdown inhibited tumorigenesis in a xenograft mouse model. Finally, we found that high level of TRIM52 expression predicted poor prognosis. In conclusion, TRIM52 knockdown inhibited cell proliferation and induced apoptosis through the activation of STAT3 signaling.

Trim47 overexpression correlates with poor prognosis in gastric cancer.

Trim47 is a member of the tripartite motif (TRIM) family that participates in many pathophysiological processes. However, the expression pattern and biological functions of Trim47 in gastric cancer (GC) remain unclear. The present study aimed to further explore the clinicopathological significance and potential prognostic role of Trim47 expression in GC. Therefore, in this study, Trim47 mRNA level was investigated in the Cancer Genome Atlas (TCGA) and Oncomine database in GC. We detected Trim47 mRNA and protein expression levels in GC and paired adjacent normal tissues. Kaplan-Meier method and Cox proportional hazard regression models were performed to analyze the survival of patients and prognostic factors. A gene set enrichment analysis (GSEA) was performed to determine the mechanism of Trim47 in GC. Our results indicated that Trim47 mRNA expression in GC tissues was significantly higher than adjacent normal tissues, as was Trim47 protein expression. Trim47 overexpression in GC tissues was significantly associated with tumor differentiation, T stage, N stage, M stage, and TNM stage. Kaplan-Meier analyses showed that high Trim47 expression was associated with worse overall survival (OS) and disease-free survival (DFS) in GC patients. Multivariate analysis confirmed that Trim47 expression was an independent prognostic factor for GC patients. Bioinformatics analysis and western blot indicated Trim47 might regulate GC through NF-κB, EMT, hypoxia, and apoptosis signaling pathway in GC. Our results show that Trim47 has the potential to serve as a novel prognostic biomarker in GC patients.

Serum MG53/TRIM72 Is Associated With the Presence and Severity of Coronary Artery Disease and Acute Myocardial Infarction.

Background: Mitsugumin 53 or Tripartite motif 72 (MG53/TRIM72), a myokine/cardiokine belonging to the tripartite motif family, can protect the heart from ischemic injury and regulate lipid metabolism in rodents. However, its biological function in humans remains unclear. This study sought to investigate the relationship between circulating MG53 levels and coronary artery disease (CAD).Methods: The concentration of MG53 was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 639 patients who underwent angiography, including 205 controls, 222 patients with stable CAD, and 212 patients with acute myocardial infarction (AMI). Logistic and linear regression analyses were used to analyze the relationship between MG53 and CAD.Results: MG53 levels were increased in patients with stable CAD and were highest in patients with AMI. Additionally, patients with comorbidities, such as chronic kidney disease (CKD) and diabetes also had a higher concentration of MG53. We found that MG53 is a significant diagnostic marker of CAD and AMI, as analyzed by logistic regression models. Multivariate linear regression models revealed that serum MG53 was significantly corelated positively with SYNTAX scores. Global Registry of Acute Coronary Events (GRACE) scores also correlated with serum MG53 levels, indicating that MG53 levels were associated with the severity of CAD and AMI after adjusting for multiple risk factors and clinical biomarkers.Conclusion: MG53 is a valuable diagnostic marker whose serum levels correlate with the presence and severity of stable CAD and AMI, and may represent a novel biomarker for diagnosing CAD and indicating the severity of CAD.

TRIM11 Prevents and Reverses Protein Aggregation and Rescues a Mouse Model of Parkinson’s Disease

Neurodegenerative diseases are characterized by the formation and propagation of protein aggregates, especially amyloid fibrils. However, what normally suppresses protein misfolding and aggregation in metazoan cells remains incompletely understood. Here, we show that TRIM11, a member of the metazoan tripartite motif (TRIM) family, both prevents the formation of protein aggregates and dissolves pre-existing protein deposits, including amyloid fibrils. These molecular chaperone and disaggregase activities are ATP independent. They enhance folding and solubility of normal proteins and cooperate with TRIM11 SUMO ligase activity to degrade aberrant proteins. TRIM11 abrogates α-synuclein fibrillization and restores viability in cell models of Parkinson's disease (PD). Intracranial adeno-associated viral delivery of TRIM11 mitigates α-synuclein-mediated pathology, neurodegeneration, and motor impairments in a PD mouse model. Other TRIMs can also function as ATP-independent molecular chaperones and disaggregases. Thus, we define TRIMs as a potent and multifunctional protein quality-control system in metazoa, which might be applied to treat neurodegenerative diseases.

Trim24 prompts tumor progression via inducing EMT in renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor originating from renal tubular epithelial cells with poor prognosis and high metastatic rate. Tripartite motif-containing 24 (Trim24) is a member of the tripartite motif (Trim) family and also a valuable oncogene, but its role in RCC remains unclear. We constructed the overexpression and knockdown of Trim24 cell lines to investigate its roles in RCC progression. CCK8, wound healing, and transwell assay were performed to determine the proliferation, migration, and invasion of RCC cell lines, respectively. Moreover, the expression of Trim24 and its clinicopathological significance were evaluated in a human RCC tissue microarray. From our results, Trim24 promoted the proliferation, migration, and invasion of RCC cells in vitro. Importantly, overexpression of Trim24 led to a significant increase in the expression levels of MMP-2, MMP-9, fibronectin, snail, vimentin, N-cadherin, and β-catenin, inducing the EMT process in turn, while the expression of these proteins was significantly downregulated when Trim24 was knocked down in ACHN cells. In addition, Trim24 was significantly upregulated in RCC, and its high expression was negatively associated with the tumor size. Trim24 might operate as an oncogene in RCC progression by inducing the EMT process, suggesting that Trim24 was a potential target for human RCC.

A Litopenaeus vannamei TRIM32 gene is involved in oxidative stress response and innate immunity

Tripartite motif (TRIM) family proteins are named by the presence of tripartite motifs in their amino terminal domains. Apart from the amino terminal, their carboxyl terminal contain variable domains which mediate diverse functions of the TRIM proteins. It had been found that TRIM proteins played important roles in distinct biological processes, such as innate immunity, anti-tumor immunity, cell cycle regulation and so on. In the present study, we cloned a TRIM32 (LvTRIM32) gene from Litopenaeus vannamei. LvTRIM32 was highly expressed in hemocytes, gills and epidermis, and subcellular localization analysis indicated that it was widely distributed in S2 cells. In vitro ubiquitination assays indicated that LvTRIM32 had E3 ubiquitin ligase activity. Results of real-time RT-PCR assay showed that LvTRIM32 was induced in shrimp hemocytes upon oxidative stress. It was also proved that the promoter activity of LvTRIM32 was enhanced by NF-E2-related factor, and knocked-down expression of LvTRIM32 depressed the expression of malic enzyme and epoxide hydrolase. Downregulated LvTRIM32 suppressed the cumulative mortality of shrimp under oxidative stress. Moreover, it was found that LvTRIM32 could be induced in shrimp hemocytes upon immunostimulation, and downregulated LvTRIM32 increased the cumulative mortality of shrimp infected with white spot syndrome virus (WSSV) or Vibrio alginolyticus. Collecting results suggested that LvTRIM32 was a member of shrimp antioxidant stress system, and it was also involved in WSSV- or V. alginolyticus-infection resistance.

TRIM21 Is Targeted for Chaperone-Mediated Autophagy during Salmonella Typhimurium Infection.

Salmonella enterica serovar Typhimurium (S Typhimurium) is a Gram-negative bacterium that induces cell death of macrophages as a key virulence strategy. We have previously demonstrated that the induction of macrophage death is dependent on the host's type I IFN (IFN-I) response. IFN-I signaling has been shown to induce tripartite motif (TRIM) 21, an E3 ubiquitin ligase with critical functions in autoimmune disease and antiviral immunity. However, the importance and regulation of TRIM21 during bacterial infection remains poorly understood. In this study, we investigated the role of TRIM21 upon S Typhimurium infection of murine bone marrow-derived macrophages. Although Trim21 expression was induced in an IFN-I-dependent manner, we found that TRIM21 levels were mainly regulated posttranscriptionally. Following TLR4 activation, TRIM21 was transiently degraded via the lysosomal pathway by chaperone-mediated autophagy (CMA). However, S Typhimurium-induced mTORC2 signaling led to phosphorylation of Akt at S473, which subsequently impaired TRIM21 degradation by attenuating CMA. Elevated TRIM21 levels promoted macrophage death associated with reduced transcription of NF erythroid 2-related factor 2 (NRF2)-dependent antioxidative genes. Collectively, our results identify IFN-I-inducible TRIM21 as a negative regulator of innate immune responses to S Typhimurium and a previously unrecognized substrate of CMA. To our knowledge, this is the first study reporting that a member of the TRIM family is degraded by the lysosomal pathway.

Expression Profile of Porcine TRIM26 and Its Inhibitory Effect on Interferon-β Production and Antiviral Response.

TRIM26, a member of the tripartite motif (TRIM) family has been shown to be involved in modulation of innate antiviral response. However, the functional characteristics of porcine TRIM26 (porTRIM26) are unclear. In this study, we used a synthesized antigen peptide to generate a polyclonal antibody against porTRIM26 with which to study the expression and function of porTRIM26. We demonstrated that polyinosinic:polycytidylic acid (poly (I:C)) stimulation and viral infection (vesicular stomatitis (VSV) or porcine reproductive and respiratory syndrome virus (PRRSV)) induce expression of porTRIM26, whereas knock-down expression of porTRIM26 promotes interferon (IFN)-β production after poly (I:C) stimulation and virus infection (VSV or PRRSV). The importance of the porTRIM26-mediated modulation of the antiviral response was also shown in VSV- or PRRSV-infected cells. In summary, these findings show that porTRIM26 has an inhibitory role in IFN-β expression and the antiviral response.

Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF-κB signaling pathway.

Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF-κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.

Expression profile of Tripartite motif family (TRIM) in human fibroblasts (NHDF) infected with porcine endogenous retrovirus (PERV).

Understanding the interactions between the microRNA (miRNA) and mRNA of genes encoding restriction factors (RFs) can lead to the development of new antiretroviral strategies aimed at providing the resistance and reducing susceptibility of human cells to potential PERV infection. Among RFs TRIM family play an important role in shaping the immune response during various stages of infection. The aim of the study was to evaluate in vitro the transcriptional profile of TRIM family genes and identify complementary miRNAs in NHDF cells infected with PERVs and induced by gram negative lipopolysacharide (LPS). Human dermal fibroblasts cells were cultured in four separate conditions- 2 monocultures: control (N), treated with LPS (NL) and 2 co-cultures with porcine PK15 cells: without LPS (NP) and treated with LPS (NLP). Bacterial LPS was used in this study as an inducer of inflammation in NHDF cells. After extraction of DNA and RNA from cells PERV infection was confirmed in co-cultures by qPCR and RTqPCR. RNA extracts served as a matrix for HGU 133A 2.0 and miRNA 2.0 microarrays to evaluate the expression profile of the selected TRIM family genes and miRNAs adequately. TRIM 2, 14, 22, and 28 were selected for the validation of HGU 133A 2.0 results. Statistical analyses were performed with the use of REST© 2009 and Genespring GX 13.0. Transcriptome Analysis Console 4.0 program (Affymetrix) was used to identify miRNAs that differentiate the studied genes in all conditions. Porcine endogenous retrovirus infection at DNA and RNA level was confirmed in NHDF cells in each of the tested groups (NP and NLP). Contamination was excluded in N and NL groups. Based on the analysis of HGU 133A 2.0 results 93 mRNA IDs of TRIM family genes differentiating analyzed conditions were selected P<.05. HGU 133A 2.0 mRNA fluorescence profile was confirmed with RTqPCR of TRIM2, TRIM14, TRIM22 and TRIM28 P<.05. TRIM14 down regulation was specific only in PERV monoinfection (group NP). In miRNA 2.0 microarray 346 miRNAs were identified as differentiating NHDF cells in all analyzed conditions, P<.05. According to the analysis with mirTAR platform and Microrna.org datatbase none of the selected miRNAs had the potential to regulate the selected genes of the TRIM family. Porcine endogenous retrovirus infection of NHDF cells is accompanied by TRIM14 down regulation suggesting TRIM14 as a possible marker of retroviral infection. None of the selected miRNAs had statistically significant potential to regulate the expression of the selected TRIMs in any of the analyzed conditions.