AGS and other tissue culture cells can unknowingly be persistently infected with PIV5; A virus that blocks interferon signalling by degrading STAT1

AbstractWhilst screening various cell lines for their ability to respond to interferon (IFN), we noted that in comparison to other tissue culture cells AGS tumour cells, which are widely used in biomedical research, had very low levels of STAT1. Subsequent analysis showed that the reason for this is that AGS cells are persistently infected with parainfluenza virus type 5 (PIV5; formally known as SV5), a virus that blocks the interferon (IFN) response by targeting STAT1 for proteasome-mediated degradation. Virus protein expression in AGS is altered in comparison to the normal pattern of virus protein synthesis observed in acutely infected cells, suggesting that the AGS virus is defective. We discuss the relevance of these results in terms of the need to screen cell lines for persistent virus infections that can alter cellular functions

Mapuera virus, a rubulavirus that inhibits interferon signalling in a wide variety of mammalian cells without degrading STATs

Mapuera virus (MPRV) is a paramyxovirus that was originally isolated from bats, but its host range remains unknown. It was classified as a member of the genus Rubulavirus on the basis of structural and genetic features. Like other rubulaviruses it encodes a V protein (MPRV/V) that functions as an interferon (IFN) antagonist. Here we show that MPRV/V differs from the IFN antagonists of other rubulaviruses in that it does not induce the proteasomal degradation of STAT proteins, key factors in the IFN signalling cascade. Rather, MPRV/V prevents the nuclear translocation of STATs in response to IFN stimulation and inhibits the formation of the transcription factor complex ISGF3. We also show that MPRV/V blocks IFN signalling in cells from diverse mammalian species and discuss the IFN response as a barrier to cross-species infections

The Nonstructural Proteins of Nipah Virus Play a Key Role in Pathogenicity in Experimentally Infected Animals

Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V−), rNiV(C−), and rNiV(W−), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V−) and rNiV(C−) were lower than the other recombinants. The rNiV(V−), rNiV(C−) and rNiV(W−) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V−) and rNiV(C−) but not the rNiV(W−) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo

The Outward Face of Massive Resistance: Segregationists’ Media Strategies during the 1950s and 1960s

to win broad support for massive resistance and construct a national countermovement against desegregation and civil rights. It reveals a protracted battle over hearts and minds between civil rights activists and massive resisters during the 1950s and 1960s through a series of detailed case studies which comprise a cumulative examination of segregationists’ efforts to influence and mobilise public opinion. Chapter 1 investigates how resisters sought to contest dominant media narratives concerning segregation by capitalising on racial strife in northern cities and selling segregation as a viable social system. Chapter 2 explores the level of consensus, collaboration, and disagreement between segregationists across the South concerning the most effective media strategy and demonstrates how public relations expertise was used to enhance their media ventures. Chapter 3 uncovers a pronounced shift in approach catalysed by Carleton Putnam, highlighting the full extent of his impact and a far-reaching, multifaceted, multimedia campaign to promote his ideas. Chapter 4 investigates segregationists’ attempts to produce dramatic photographic and cinematic imagery to recalibrate public perception of the civil rights movement, the federal government, and their combined efforts to enforce desegregation and civil rights. The thesis evaluates the effectiveness of resisters’ manifold attempts to harness different forms of mass media, revealing both their successes and failures. It uncovers how some of the most savvy strategists found ways to constrain the civil rights movement and assesses how they positioned some aspects of segregationist thought as part of a broader, national conservative ideology. By tracing the ebb and flow of segregationist media strategies, it offers new and important insights into the nature and trajectory of massive resistance, the successes and shortcomings of the civil rights movement, and the development of a new national conservatism.</div

Relationships and host range of human, canine, simian and porcine isolates of Simian Virus 5 (Parainfluenza virus 5).

Sequence comparison of the V/P and F genes of 13 human, canine, porcine and simian isolates of simian virus 5 (SV5) revealed a surprising lack of sequence variation at both the nucleotide and amino acid levels (0-3%), even though the viruses were isolated over 30 years and originated from countries around the world. Furthermore, there were no clear distinguishing amino acid or nucleotide differences among the isolates that correlated completely with the species from which they were isolated. In addition, there was no evidence that the ability of the viruses to block interferon signalling by targeting STAT1 for degradation was confined to the species from which they were isolated. All isolates had an extended cytoplasmic tail in the F protein, compared with the original W3A and WR monkey isolates. Sequence analysis of viruses that were derived from human bone-marrow cells isolated in London in the 1980s revealed that, whilst they were related more closely to one another than to the other isolates, they all had identifying differences, suggesting that they were independent isolates. These results therefore support previous data suggesting that SV5 can infect humans persistently, although the relationship of SV5 to any human disease remains highly contentious. Given that SV5 has been isolated on multiple occasions from different species, it is proposed that the term simian virus 5 is inappropriate and suggested that the virus should be renamed parainfluenza. virus 5.</p