Paramyxovirus Accessory Proteins as Interferon Antagonists

Abstract

A new role of the Paramyxovirus accessory proteins has been uncovered. The P gene of the subfamily Paramyxovirinae encodes accessory proteins including the V and/or C protein by means of pseudotemplated nucleotide addition (RNA editing) or by overlapping open reading frame. The Respirovirus (Sendai virus and human parainfluenza virus (hPIV)3) and Rubulavirus (simian virus (SV)5, SV41, mumps virus and hPIV2) circumvent the interferon (IFN) response by inhibiting IFN signaling. The responsible genes were mapped to the C gene for SeV and the V gene for rubulaviruses. On the other hand, wild type measles viruses isolated from clinical specimens suppress production of IFN, although responsible viral factors remain to be identified. Both human and bovine respiratory syncytial viruses (RSVs) counteract the antiviral effect of IFN with inhibiting neither IFN signaling nor IFN production. Bovine RSV NSI and NS2 proteins cooperatively antagonize the antiviral effect of IFN. Studies on the molecular mechanism by which viruses circumvent the host IFN response will not only illustrate co-evolution of virus strategies of immune evasion but also provide basic information useful for engineering novel antiviral drugs as well as recombinant live vaccine.

Avian metapneumovirus infection of chicken and turkey tracheal organ cultures: comparison of virus–host interactions

“…Both RSV and hMPV were shown to interfere with the IFN cascade and to inhibit IFN production in the lung (Guerrero-Plata et al, 2005). It is suggested that the non-structural proteins NS1 and NS2 of RSV and the G protein of hMPV are responsible for the resistance to IFN-α, by inhibiting the effect of antiviral proteins including MxA or by targeting signalling pathways such as the RIG-I-dependent gene transcription (Schlender et al, 2000;Gotoh et al, 2001;Leyrat et al, 2014). We were able to show that the down-regulation of IFN-α mRNA expression was more prominent in CTOC than in TTOC.…”

The STAT2 Activation Process Is a Crucial Target of Sendai Virus C Protein for the Blockade of Alpha Interferon Signaling

“…The former conclusion was drawn from experimental results achieved mainly with mutated recombinant SeV-infected cells, in which the anti-IFN ability of the mutant C proteins would be affected by many factors, including other viral proteins, autocrine IFN associated with infection, and the expression level of the mutant C protein at the time of IFN treatment. It is possible that these factors might have led to the discrepancy (16,17). In contrast to the STAT degradationindependent mechanism presented here, Garcin et al emphasized the degradation of STAT1 in SeV-infected MEF cells as an SeV blocking mechanism for IFN signaling and attempted to find the common denominator between functions of SeV C protein and rubulavirus V proteins (10,11,13,30).…”

“…This finding had suggested crucial roles of the V and C proteins in a virus life cycle, although their roles had remained an enigma for a long time. Several lines of evidence have accumulated, however, demonstrating that the accessory proteins form a group of antagonists against the host immune system (9,(15)(16)(17). The Paramyxovirinae family contains three genera: Rubulavirus, Respirovirus, and Morbillivirus.…”

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

“…However, there is increasing evidence that P, W, or C proteins of paramyxoviruses including NiV, MeV, and SeV play important roles in IFN antagonism by distinct mechanisms. Thus, it seems that most if not all P gene accessory proteins have evolved for roles in immune evasion as important pathogenicity factors [24][25][26][27][28] . Consistent with important roles in infection, V proteins show high conservation in the unique C-terminal region ( Figure 2) [29][30][31] , including absolute conservation of seven conserved cysteine residues and a histidine, which form a zinc-finger domain (highlighted in Figure 2).…”