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Host Cell Restriction Factors of Paramyxoviruses and Pneumoviruses - PubMed

  • ️Wed Jan 01 2020

Review

Host Cell Restriction Factors of Paramyxoviruses and Pneumoviruses

Rubaiyea Farrukee et al. Viruses. 2020.

Abstract

The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.

Keywords: innate; interferon-stimulated gene; paramyxovirus; pneumovirus; replication; restriction factor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Structure and Replication of Paramyxo- and Pneumoviruses. Paramyxo- and pneumoviruses share a common structure comprising surface fusion (F) and attachment (H/HN/G) proteins (and an additional small hydrophobic (SH) protein for some) located in a host-derived lipid bilayer. Beneath this layer, the matrix (M) protein forms a shell within which is contained the ribonucleocapsid, comprising the phosphoprotein (P) and Large (L) polymerase subunit, as well as a negative-sense, single-stranded RNA genome bound by nucleoprotein (NP) in the form of ribonculeoproteins (RNPs). (1) Upon attachment to the host cell via H/HN/G proteins, paramyxovirus and pneumovirus entry is facilitated by the F protein, releasing the ribonucleocapsid into the cytosol. Pneumoviruses may additionally enter the cell via endocytosis. CH25H, IFITM1 and IFITM3 have been identified to inhibit entry of some viruses. (2) Viral RNA is then transcribed to mRNA and the viral proteins translated, with the glycoproteins (H/HN/G, F and SH) travelling through the ER to the Golgi before reaching the cell surface. Viral RNA is additionally transcribed to produce a positive-sense antigenome, which is replicated to give negative-sense genomic RNA. Restriction factors known to inhibit these stages of virus replication include, ABOBEC3G, OAS1, OAS2, MxA, IFIT1, PKR, ZAP, ISG15, GBP2, and GBP5. The exact step in the virus replication process inhibited by IDO1 and TDRD7 has not been identified. (3) After genomic replication, RNA associates with the NP to form RNPs, as well as the P and L proteins, and traffics to the cell membrane where it interacts with M protein. Once this ribonucleocapsid is assembled with the surface proteins, newly-formed virions are released by budding. The restriction factors tetherin and viperin can interfere with assembly and budding.

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