TRIM22. A Multitasking Antiviral Factor

Figures

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  Figure 1. (A) Structural organization of the HIV-1 promoter. HIV-1 transcription starts at the promoter region in the 5′ LTR. Processive HIV-1 transcription is driven by the Tat protein that recruits the p-TEFb complex to the TAR RNA. pTEFb promotes the phosphorylation of the RNA Pol II, enabling the elongation of the viral transcripts. Upstream of the initiation of transcription (+1), three Sp1 and two NF-kB binding sites control the levels of basal transcription and response to inflammatory signals, respectively. (B) TRIM22 inhibits HIV-1 basal transcription by preventing Sp1 binding to the HIV-1 promoter, thus contributing to the maintenance of latent HIV-1 infection.

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  Figure 2. Evolution from pandemic to seasonal IAV has shaped TRIM22 restriction. Pandemic viruses are resistant to TRIM22 inhibition as their NP is endowed with four arginine (R) residues that progressively mutate into lysine (K) residues, becoming the target of the U3 ubiquitin ligase activity of TRIM22. The transition of R into K is dependent on viral polymerase errors that generate viral quasispecies either characterized by one, two, three or four K residues. However, a bottleneck of transmission favors the emergence of an IAV NP susceptible to TRIM22 restriction. This phenomenon is likely related to the general rule of viral evolution which endows the virus with the ability to become more transmissible and less pathogenic.