Browsing by Subject "virus-host interaction"

Sort by: Order: Results:

Now showing items 1-5 of 5
  • Ianevski, Aleksandr; Yao, Rouan; Zusinaite, Eva; Lysvand, Hilde; Oksenych, Valentyn; Tenson, Tanel; Bjoras, Magnar; Kainov, Denis (2021)
    Background: Every year, millions of people are hospitalized and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among the elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection and thus contribute to the morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds from a list of commonly prescribed medicines. Then, we constructed a drug-target interaction network and identified the potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on the viability, transcription, and metabolism of mock- and FLUAV-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that drugs such as atorvastatin, candesartan, and hydroxocobalamin could target and modulate FLUAV-host cell interaction. In vitro experiments showed that at non-cytotoxic concentrations, these compounds affected the transcription and metabolism of FLUAV- and mock-infected cells. Conclusion: Many commonly prescribed drugs were found to modulate FLUAV-host cell interactions in silico and in vitro and could therefore affect their interplay in vivo, thus contributing to the morbidity and mortality of patients with influenza virus infections.
  • Bösl, Korbinian; Ianevski, Aleksandr; Than, Thoa T.; Andersen, Petter I.; Kuivanen, Suvi; Teppor, Mona; Zusinaite, Eva; Dumpis, Uga; Vitkauskiene, Astra; Cox, Rebecca J.; Kallio-Kokko, Hannimari; Bergqvist, Anders; Tenson, Tanel; Merits, Andres; Oksenych, Valentyn; Bjørås, Magnar; Anthonsen, Marit W.; Shum, David; Kaarbø, Mari; Vapalahti, Olli; Windisch, Marc P.; Superti-Furga, Giulio; Snijder, Berend; Kainov, Denis; Kandasamy, Richard K. (2019)
    Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.
  • Mäntynen, Sari; Sundberg , Lotta-Riina; Oksanen, Hanna Maarit; Poranen, Minna Marjetta (2019)
    Half a century of research on membrane-containing phages has had a major impact on virology, providing new insights into virus diversity, evolution and ecological importance. The recent revolutionary technical advances in imaging, sequencing and lipid analysis have significantly boosted the depth and volume of knowledge on these viruses. This has resulted in new concepts of virus assembly, understanding of virion stability and dynamics, and the description of novel processes for viral genome packaging and membrane-driven genome delivery to the host. The detailed analyses of such processes have given novel insights into DNA transport across the protein-rich lipid bilayer and the transformation of spherical membrane structures into tubular nanotubes, resulting in the description of unexpectedly dynamic functions of the membrane structures. Membrane-containing phages have provided a framework for understanding virus evolution. The original observation on membrane-containing bacteriophage PRD1 and human pathogenic adenovirus has been fundamental in delineating the concept of viral lineages, postulating that the fold of the major capsid protein can be used as an evolutionary fingerprint to trace long-distance evolutionary relationships that are unrecognizable from the primary sequences. This has brought the early evolutionary paths of certain eukaryotic, bacterial, and archaeal viruses together, and potentially enables the reorganization of the nearly immeasurable virus population (similar to 1 x 10(31)) on Earth into a reasonably low number of groups representing different architectural principles. In addition, the research on membrane-containing phages can support the development of novel tools and strategies for human therapy and crop protection.
  • Pavel, Alisa; del Giudice, Giusy; Federico, Antonio; Di Lieto, Antonio; Kinaret, Pia A. S.; Serra, Angela; Greco, Dario (2021)
    The COVID-19 disease led to an unprecedented health emergency, still ongoing worldwide. Given the lack of a vaccine or a clear therapeutic strategy to counteract the infection as well as its secondary effects, there is currently a pressing need to generate new insights into the SARS-CoV-2 induced host response. Biomedical data can help to investigate new aspects of the COVID-19 pathogenesis, but source heterogeneity represents a major drawback and limitation. In this work, we applied data integration methods to develop a Unified Knowledge Space (UKS) and used it to identify a new set of genes associated with SARS-CoV-2 host response, both in vitro and in vivo. Functional analysis of these genes reveals possible long-term systemic effects of the infection, such as vascular remodelling and fibrosis. Finally, we identified a set of potentially relevant drugs targeting proteins involved in multiple steps of the host response to the virus.
  • Ylosmaki, Leena; Fagerlund, Riku; Kuisma, Inka; Julkunen, Ilkka; Saksela, Kalle (2016)
    The non-structural protein-1 (NS1) of many influenza A strains, especially those of avian origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk (Chicken tumor virus number 10 (CT10) regulator of kinase) and Crk-like adapter protein (CrkL). This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol 3-kinase (PI3K), but additional effects on the host cell physiology may exist. Here we show that NS1 can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif.