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J Virol. 2011 May;85(10):5183-96. doi: 10.1128/JVI.02302-10. Epub 2011 Feb 23.

TRIM22 inhibits HIV-1 transcription independently of its E3 ubiquitin ligase activity, Tat, and NF-kappaB-responsive long terminal repeat elements.

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Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation, and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy.


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 ∼7-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-κB 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-κB-independent LTR-driven transcription.

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