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.

Understanding the causes of infectious disease to facilitate better control requires observational and experimental studies. Often these must be conducted at many scales such as at the molecular, cellular, organism, and population level. Studies need to consider both intrinsic and extrinsic factors affecting the pathogen/host interaction. They also require a combination of study methods covered by disciplines such as pathology, epidemiology, microbiology, and ecology. Therefore, it is important that disciplines work together when designing and conducting studies. Finally, we need to integrate and interpret data across levels and disciplines to better formulate control strategies. This requires another group of specialists with broad crossdisciplinary training in epidemiology and an ability to readily work with others.
Determining Causality and Controlling Disease is Based on Collaborative Research involving Multidisciplinary Approaches

Background: The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an "avian-like" H1N1 virus by an experimental infection study. Methods: Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an "avian-like" H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European "avian-like" H1-gene and a European "swine-like" N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish "avian-like" H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. The "avian-like" H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine "avian-like" H1N1 and H3N2. The Danish H1N2 has an "avian-like" H1 and differs from most other reported H1N2 viruses in Europe and North America/Asia, which have H1-genes of human or "classical-swine" origin, respectively. The variant seems, however, also to be circulating in countries like Sweden and Italy. The infection dynamics of the reassorted "avian-like" H1N2 is similar to the older "avian-like" H1N1 subtype.
Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark

In herpes simplex virus 1 (HSV-1)-infected cells, G4s are massively present during viral replication. We here aimed at investigating the possibility to target the HSV-1 G4s by a core extended naphtalene diimide (c-exNDI) G4 ligand. Biophysical and biomolecular analysis proved that c-exNDI stabilized the HSV-1 G4s in a concentration dependent manner. In MS competition assays, c-exNDI preferentially recognized HSV-1 G4s over cellular telomeric G4s, the most represented G4s within cells; other less abundant cellular G4s were also recognized. Treatment of HSV-1 infected cells with c-exNDI at low nanomolar concentrations induced significant virus inhibition with no cytotoxicity. The mechanism of action was ascribed to G4-mediated inhibition of viral DNA replication, with consequent impairment of viral genes transcription. Our data suggest that the observed potent antiviral activity and low cytotoxicity mainly depend on a combination of c-exNDI affinity for HSV-1 G4s and their massive presence during infection. HSV-1 G4s may thus represent new effective antiviral targets: the fact that no current antiherpetic drug exploits them and their presence at the viral genome, responsible for both active and latent HSV infections, makes them particularly attracting. G-quadruplexes (G4s) are nucleic acids secondary structures that may form in single-stranded G-rich sequences under physiological conditions 1 . Four Gs bind via Hoogsteen-type hydrogen bonds base-pairing to yield G-quartets, which stack to form the G4. The presence of K + cations specifically supports G4 formation and stability 2 . Based on the strand orientation, G4s can adopt three main topologies: parallel, antiparallel, and hybrid-type structures. In eukaryotes, G4s have been shown to be involved in key regulatory roles, including transcriptional regulation of gene promoters and enhancers, translation, chromatin epigenetic regulation, DNA recombination 3-7 . Expansion of G-quadruplex-forming motifs has been associated with relevant human neurological disorders 4, 8, 9 . Formation of G4s in vivo has been consolidated by the discovery of cellular proteins that specifically recognize G4s 10, 11 and the development of G4 specific antibodies 12, 13 . Recently, the presence of G4s in viruses and their involvement in virus key steps has been provided 14 . G4s have been implicated in pathogenic mechanisms of the human immunodeficiency virus, where functionally significant G4s have been identified 5, 11, 15-17 and stabilized by G4 ligands with consequent antiviral effects 5, 18, 19 . G4s have been reported in the SARS coronavirus 20 , the human papilloma, Zika, Ebola and hepatitis C virus genome 21-24 . Among herpesviruses, RNA G4s have been implicated in the regulation of DNA replication and translation of the Epstein-Barr virus 25, 26 . We have shown that the herpes simplex virus 1 (HSV-1) possesses several repeats of important G4-forming sequences, which could be stabilized by a G4 ligand with inhibition of viral DNA replication 27 . In addition, HSV-1 G4s, visualized with the aid of a G4-specific antibody in infected cells 12 , were shown to form massively in the cell nucleus, peak during viral replication and localize according to the viral genome intracellular movements 28 . The involvement of G4 structures in several human diseases propelled the development of small molecules directed against G4s 7, 29 . However, only very few have been tested against viruses, i.e. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 2341 |

A core extended naphtalene diimide G-quadruplex ligand potently inhibits herpes simplex virus 1 replication OPEN