In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Several polypeptide products of MHV-A59 ORF 1 a were characterized in MHV-A59 infected DBT cells, using antisera directed against fusion proteins encoded in the first 6.5 kb of ORFla. These included the previously identified N-terminal ORF 1 a product, ~28, as well as 290-, 240-, and 50-kDa polypeptides. P28 was always detected as a discrete band without larger precursors, suggesting rapid cleavage of p28 immediately after its synthesis. Once p28 was cleaved there was little degradation of the protein over a 2-hr period. The intracellular cleavage of p28 was not inhibited by the protease inhibitor leupeptin, in contrast to results obtained during in vitro translation of genome RNA (Denison and Perlman, 1986). These data suggest that different protease activities may be responsible for the cleavage of p28 in vitro and in Go. The 290-kDa protein was an intermediate cleavage product derived from a precursor of greater than 400 kDa. The 290-kDa product was subsequently cleaved into secondary products of 50 and 240 kDa. The intracellular cleavage of the 290-kDa polypeptide was inhibited by leupeptin at concentrations which did not inhibit the early cleavage of p28 or the cleavage of the 290-kDa product from its larger polyprotein precursor. In the presence of zinc chloride, a product of >320 kDa was detected, which appears to incorporate p28 at its amino terminus. This suggests that at least two protease activities may be necessary for processing of ORFl a proteins, one of which cleaves p28 and is sensitive to zinc chloride but resistant to leupeptin, and the other which cleaves the 290-kDa precursor and is sensitive to both inhibitors. Both the 290-and 240-kDa proteins should contain sequences predicted to encode two papain-like prOtesS? activities. 0 1992 Academic PVE.S. Inc.
Intracellular Processing of the N-Terminal ORF la Proteins of the Coronavirus MHV-A59 Requires Multiple Proteolytic Events

Attenuated viral vaccines can be generated by targeting essential pathogenicity factors. We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the nonstructural protein 1 (nsp1). In cell culture, nsp1 of mouse hepatitis virus (MHV), like its SARS-coronavirus homolog, strongly reduced cellular gene expression. The effect of nsp1 on MHV replication in vitro and in vivo was analyzed using a recombinant MHV encoding a deletion in the nsp1-coding sequence. The recombinant MHV nsp1 mutant grew normally in tissue culture, but was severely attenuated in vivo. Replication and spread of the nsp1 mutant virus was restored almost to wild-type levels in type I interferon (IFN) receptor-deficient mice, indicating that nsp1 interferes efficiently with the type I IFN system. Importantly, replication of nsp1 mutant virus in professional antigen-presenting cells such as conventional dendritic cells and macrophages, and induction of type I IFN in plasmacytoid dendritic cells, was not impaired. Furthermore, even low doses of nsp1 mutant MHV elicited potent cytotoxic T cell responses and protected mice against homologous and heterologous virus challenge. Taken together, the presented attenuation strategy provides a paradigm for the development of highly efficient coronavirus vaccines.
Coronavirus Non-Structural Protein 1 Is a Major Pathogenicity Factor: Implications for the Rational Design of Coronavirus Vaccines

Lack of disease surveillance in small companion animals worldwide has contributed to a deficit in our ability to detect and respond to outbreaks. In this paper we describe the first real-time syndromic surveillance system that conducts integrated spatio-temporal analysis of data from a national network of veterinary premises for the early detection of disease outbreaks in small animals. We illustrate the system's performance using data relating to gastrointestinal disease in dogs and cats. the data consist of approximately one million electronic health records for dogs and cats, collected from 458 UK veterinary premises between March 2014 and 2016. For this illustration, the system predicts the relative reporting rate of gastrointestinal disease amongst all presentations, and updates its predictions as new data accrue. The system was able to detect simulated outbreaks of varying spatial geometry, extent and severity. The system is flexible: it generates outcomes that are easily interpretable; the user can set their own outbreak detection thresholds. the system provides the foundation for prompt detection and control of health threats in companion animals. Surveillance systems have been developed globally for animal and/or public health purposes, facilitating the prevention and control of disease or infection nationally and regionally. During the past decade, the emergence of new diseases 1 and the increasing threat of bio-terrorism have motivated the development of syndromic surveillance systems in public health focused on the early detection of health threats that require effective public health action 2,3 . Syndromic surveillance uses health-related data that precedes diagnosis. Although data of this kind are less specific than data from confirmed diagnoses they are typically more timely, which is an important consideration for real-time or near-real-time analysis and interpretation 4 . In veterinary medicine the development of systems for early health-event detection has followed a similar path to that previously taken in public health 5 . A recent inventory of current and planned European veterinary syndromic surveillance systems showed wide interest in European countries for syndromic surveillance, but also highlighted the novelty of this field 6 . Small companion animal populations largely lack co-ordinated national and international disease surveillance. This has produced a deficit in our understanding of the dynamics and burden of the full range of endemic/ emerging diseases in companion animals and leaves these populations susceptible to the emergence of health threats. Lack of disease surveillance also has implications for human health, as approximately 75 percent of new and emerging diseases are zoonotic 7 . However, as health records become digitised in veterinary practices they become more available for research 8 , providing an opportunity to improve companion animal syndromic surveillance in clinical settings and the possibility of linking this with human syndromic surveillance. Recently, electronic syndromic surveillance data on companion animals has become available in real-time on a national scale www.nature.com/scientificreports www.nature.com/scientificreports/ without adjustment, on the grounds that multiple visits occurring within a short time period (e.g. within a few days) would likely indicate a more serious illness episode. Data summary. Of the 1,211,326 consultations collected between 1 st March 2014 and 29 th February 2016, 72.3% were for dogs and 27.7% for cats. In 80.7% of all consultations a valid age, breed-status (purebred or crossbred) and owner's full postcode were recorded; this subset of data is used for model selection and the basis for simulations. Gastrointestinal disease accounted for 4.0% of all presentations, amongst which 91.5% were recorded between Monday and Friday. Amongst animals presenting for GI disease, there was not a notable gender bias; 48.5% of dog consultations and 50.6% of cat consultations with a recorded sex were female. Where the breed-status was identified, 84.9% of dog GI disease consultations and 17.2% of cat GI disease consultations were purebreds. In animals with a date of birth recorded within the range 0 to 25 years, 65.4% of dog GI disease consultations and 47.4% of cat GI disease consultations were under eight years. The age profile of dogs and cats presenting for GI disease at SAVSNET veterinary premises stratified by sex and breed-status is shown in Table 1 . Data for the two species were analysed separately. We used the pet owner's home postcode to assign a measure of deprivation to each owner using the most recent English 17 , Scottish 18 and Welsh 19 Indices of Multiple Deprivation (IMD) produced by their respective governments. A detailed description of how each government has developed their own measure of deprivation can be found elsewhere [20] [21] [22] . The three country-specific IMD measures are not directly comparable. We therefore included country as a three-level factor and rescaled the ranks of each country's set of IMD scores to the range 0 to 1. For example, if for England the maximum rank was 32,000 and a location had rank 100 then the owner IMD explanatory variable would be assigned a value of 100/32,000. • Scheme 1: The outbreak only affects the central premise of each set. For each, we simulate outbreaks of different severities, in which the probability of a case is 0.1, 0.15 or 0.2. This gives a total of 9 scenarios. • Scheme 2: The outbreak affects the central premise and all of its neighbouring premises. This leads to another 6 separate scenarios, as Schemes 1 and 2 are identical for the sparse set. Scientific RepoRtS | (2019) 9:17738 | https://doi.

6 NIHR Health Protection Research Unit in Gastrointestinal Infections