TRIM22: A Diverse and Dynamic Antiviral Protein

Hattlmann, Clayton J.; Kelly, Jenna N.; Barr, Stephen D.

doi:10.1155/2012/153415

Cited by 50 publications

(57 citation statements)

References 63 publications

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“…19 When 293T or COS7 cells were transfected with human TRIM22 tagged with GFP, TRIM22 was localized in the cytoplasm. 19 . TRIM22 was colocalized with NS5A in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…19,22,23 Moreover, in the serum-starved U2OS cell line, TRIM22 was localized in both the nucleus and cytoplasm. 19,24,25 Gao and colleagues observed that TRIM22 was mainly localized in the nucleus of HepG2 cells when it suppresses HBV survival. 13 The discrepancy in localization compared to our present study may be due to the different cell lines we used (Huh-7 cell lines).…”

Section: Ifn-a-induced Trim22 Interrupts Hcv Replicationmentioning

confidence: 94%

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Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

et al. 2015

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TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNa) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein. NS5A is important for HCV replication and for resistance to IFNa therapy. During the first 24 h following the initiation of IFNa treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFNa-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNa treatment and plays an important role in controlling HCV replication in vitro.

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“…19 When 293T or COS7 cells were transfected with human TRIM22 tagged with GFP, TRIM22 was localized in the cytoplasm. 19 . TRIM22 was colocalized with NS5A in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Section: Ifn-a-induced Trim22 Interrupts Hcv Replicationmentioning

confidence: 94%

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

et al. 2015

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“…However, TRIM E3 ligases are a heterogeneous group of proteins, and little is known about the contribution of specific members of this family to antiviral activity in vivo and the factors that may contribute to differential expression or effectiveness in blocking viral replication (15,36,37). We hypothesized that TRIM E3 ligases, as a component of the innate immune system, may play a significant role in blocking retroviral infection during the early phases of infection and in a remote anatomical site likely deficient in a robust adaptive immune system.…”

Section: Discussionmentioning

confidence: 99%

TRIM5α and TRIM22 Are Differentially Regulated According to HIV-1 Infection Phase and Compartment

Singh

Patel

Mureithi

et al. 2014

J Virol

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The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5␣ and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5␣, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (P < 0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5␣ than did PBMCs from primary infection or HIV-1-uninfected PBMCs (P ‫؍‬ 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (P ‫؍‬ 0.001) and TRIM5␣ (P ‫؍‬ 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (r ‫؍‬ ؊0.40; P ‫؍‬ 0.04). In vitro, IFN-I and, rarely, proinflammatory cytokines induced TRIM5␣ and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4 ؉ lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5␣ and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases in vivo. IMPORTANCEType I interferon-inducible TRIM E3 ligases are a family of intracellular proteins with potent antiviral activities mediated through diverse mechanisms. However, little is known about the contribution of these proteins to antiviral immunity in vivo and how their expression is regulated. We show here that TRIM5␣ and TRIM22, two prominent members of the family, have different expression patterns in vivo and that the expression pattern depends on HIV-1 infection status and phase. Furthermore, expression differs in peripheral blood versus central nervous system anatomical sites of infection. Only TRIM22 expression correlated negatively with HIV-1 viral load, but gene silencing of both proteins enhances HIV-1 infection of target cells. We report subtle differences in TRIM5␣ and TRIM22 gene induction by IFN-I and proinflammatory cytokines in CD4 ؉ lymphocytes, monocytes, and neuronal cells. This study enhances our understanding of antiviral immunity by intrinsic antiviral factors and how their expression is determined.

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“…In particular, many members of the TRIM family induced in response to IFNs are associated with innate immunity and antiviral defence 24. Among them, TRIM22, one of the closest paralogs of TRIM5α, displays antiretroviral activity similar to that of TRIM5α 25. Several studies have found that TRIM22 inhibits the transcription and replication of HIV through suppression of its long terminal repeat and disruption of the intracellular trafficking of the viral Gag protein 26 27.…”

Section: Introductionmentioning

confidence: 99%

Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5′-UTR of TRIM22

Lim

Park

Kim

et al. 2017

Gut

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TRIM22: A Diverse and Dynamic Antiviral Protein

Cited by 50 publications

References 63 publications

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

TRIM5α and TRIM22 Are Differentially Regulated According to HIV-1 Infection Phase and Compartment

Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5′-UTR of TRIM22

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