Association of TRIM22 with the Type 1 Interferon Response and Viral Control during Primary HIV-1 Infection

Singh, Ravesh; Gaiha, Gaurav D.; Werner, Lise.; McKim, Kevin J.; Mlisana, Koleka; Luban, Jeremy; Walker, Bruce D.; Karim, Salim Safurdeen. Abdool; Brass, Abraham L.; Ndung’u, Thumbi

doi:10.1128/jvi.01810-10

Cited by 74 publications

(58 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a prospective cohort study of HIV-1-negative individuals at high risk for HIV-1 infection, we showed that elevated expression levels of TRIM5␣ were associated with decreased susceptibility to HIV-1 infection (25). We subsequently found that TRIM22 but not TRIM5␣, IFN-␣, IFN-␤, or myxovirus resistance protein A (MxA) expression correlated negatively with plasma viral load and positively with CD4 ϩ T cell counts in primary HIV-1 infection, suggesting a protective, antiviral role in vivo (17).…”

mentioning

confidence: 67%

“…TRIM5␣ is responsible for species-specific postentry restriction of retroviruses such as murine leukemia N-tropic virus (N-MLV) and HIV-1 in primate cells (13,14). TRIM22 is also induced by IFN-I and inhibits viral replication by interfering with viral gene transcription and virion assembly (15)(16)(17)(18)(19). Genetic association studies have demonstrated that polymorphic variants of the human TRIM5␣ gene are associated with reduced susceptibility to HIV infection or are overrepresented among HIV-negative individuals compared to HIV-positive ones (20,21), suggesting that human TRIM5␣ may have some protective role against HIV-1 infection.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Singh

Patel

Mureithi

et al. 2014

J Virol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 67%

mentioning

confidence: 99%

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

Singh

Patel

Mureithi

et al. 2014

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Once its physiological expression in relevant primary target cells for HIV infection is defined, as recently shown for primary human peripheral blood mononuclear cells (PBMC) (54) and as previously investigated at the RNA level in primary human monocyte-derived macrophages and PBMC (12), TRIM22 could represent a potential target for pharmacological approaches aimed at reactivating latent HIV infection in order to expose these cells to immunological surveillance and curtailing the viral reservoirs unaffected by current antiretroviral therapy. Furthermore, a recent report has shown that TRIM22 expression, but not huTRIM5␣ expression, in the PBMC of HIV-1 recent seroconverters positively correlated with type I IFN and CD4 ϩ T cell counts, whereas a negative correlation was shown between TRIM22 expression and plasma viral load, emphasizing the potential role of TRIM22 as an antiviral response molecule in vivo (62). Thus, TRIM22 could be harnessed for antiviral control in the critical acute phase of HIV infection and used to counteract disease progression in infected individuals.…”

Section: Discussionmentioning

confidence: 98%

TRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements

Kajaste‐Rudnitski

Marelli

Pultrone

et al. 2011

J Virol

Self Cite

115

View full text Add to dashboard Cite

Previous studies identified clones of the U937 promonocytic cell line that were either permissive or nonpermissive for human immunodeficiency virus type 1 (HIV-1) replication. These clones were investigated further in the search for host restriction factors that could explain their differential capacity to support HIV-1 replication. Among known HIV-1 restriction factors screened, tripartite motif-containing protein 22 (TRIM22) was the only factor constitutively expressed in nonpermissive and absent in permissive U937 cells. Stable TRIM22 knockdown (KD) rescued HIV-1 long-terminal-repeat (LTR)-driven transcription in KD-nonpermissive cells to the levels observed in permissive cells. Conversely, transduction-mediated expression of TRIM22 in permissive cells reduced LTR-driven luciferase expression by ϳ7-fold, supporting a negative role of TRIM22 in HIV-1 transcription. This finding was further confirmed in the human T cell line A3.01 expressing TRIM22. Moreover, overexpression of TRIM22 in 293T cells significantly impaired basal and phorbol myristate acetate-ionomycin-induced HIV-1 LTR-driven gene expression, whereas inhibition of tumor necrosis factor alpha-induced viral transcription was a consequence of lower basal expression. In agreement, TRIM22 equally inhibited an LTR construct lacking the tandem NF-B binding sites. In addition, TRIM22 did not affect Tat-mediated LTR transactivation. Finally, these effects were independent of TRIM22 E3 ubiquitin-ligase activity. In the context of replication-competent virus, significantly higher levels of HIV-1 production were observed in KD-nonpermissive versus control nonpermissive U937 cells after infection. In contrast, lower peak levels of HIV-1 replication characterized U937 and A3.01 cells expressing TRIM22 versus their control transduced counterpart. Thus, nuclear TRIM22 significantly impairs HIV-1 replication, likely by interfering with Tat-and NF-B-independent LTR-driven transcription.

show abstract

“…Its close homologue, TRIM22, functions to inhibit HIV budding from infected cells [53]. Recent evidence also demonstrates an inverse correlation between viral load and expression of TRIM22, reinforcing its role as a potent restriction factor against HIV in vivo [54]. A genetic study investigating the role of human endogenous retroviruses (HERV) in multiple sclerosis (MS), demonstrated an inverse correlation between SNPs in TRIM5α and MS.…”

Section: Trim5α and Trim22mentioning

confidence: 99%

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

2011

View full text Add to dashboard Cite

Association of TRIM22 with the Type 1 Interferon Response and Viral Control during Primary HIV-1 Infection

Cited by 74 publications

References 47 publications

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

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

TRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

Contact Info

Product

Resources

About