Emerging Role of PYHIN Proteins as Antiviral Restriction Factors

Abstract

Innate immune sensors and restriction factors are cellular proteins that synergize to build an effective first line of defense against viral infections. Innate sensors are usually constitutively expressed and capable of detecting pathogen-associated molecular patterns (PAMPs) via specific pattern recognition receptors (PRRs) to stimulate the immune response. Restriction factors are frequently upregulated by interferons (IFNs) and may inhibit viral pathogens at essentially any stage of their replication cycle. Members of the Pyrin and hematopoietic interferon-inducible nuclear (HIN) domain (PYHIN) family have initially been recognized as important sensors of foreign nucleic acids and activators of the inflammasome and the IFN response. Accumulating evidence shows, however, that at least three of the four members of the human PYHIN family restrict viral pathogens independently of viral sensing and innate immune activation. In this review, we provide an overview on the role of human PYHIN proteins in the innate antiviral immune defense and on viral countermeasures.

Replication competent HIV-guided CRISPR screen identifies antiviral factors including targets of the accessory protein Nef

“…6i ). IFI16 has been reported to inhibit viral pathogens including HIV-1 by a variety of mechanisms and has also been proposed to play roles in innate sensing of viral pathogens 63 – 65 . Our finding that the inhibitory activity of IFI16 is not only evaded by an additional NF-κB binding site in the LTR of currently dominating clade C viruses 52 but also counteracted by Nef further supports an important role of this antiviral factor.…”

Viral manipulation of host cell necroptosis and pyroptosis

“…An ever-expanding group of innate immune sensors initiate inflammasome activation and trigger pyroptosis upon viral infection. These include the NOD-like receptor and pyrin domain containing (NLRP) family members NLRP1 and NLRP3 and the HIN200-containing proteins Absent in melanoma 2 (AIM2) and IFN-γ inducible protein 16 (IFI16; p204 in mice) [5,[71][72][73][74]. While AIM2 and IFI16 trigger pyroptosis upon recognition of viral dsDNA, both NLRP1 and NLRP3 seem to detect viral activities rather than directly sensing viral molecules in a process called effector-triggered immunity.…”

Immunological Insights of Bat Coexistence with Viruses and beyond: A Holistic Review

“…An amino acid substitution (serine at S538) has been reported in the STING protein of bats, and studies suggest that this mutation might dampen STING-dependent IFN activation [25]. It can inhibit viral pathogens, possibly by restricting its transcription, independent of viral immune sensing and induction of IFN [50]. Being a sensor of viral dsRNA motifs, RIG-I induces the expression of type I IFNs [51].…”