Systems virology: host-directed approaches to viral pathogenesis and drug targeting

Abstract

Preface High-throughput molecular profiling and computational biology are changing the face of virology, providing a new appreciation of the importance of the host in viral pathogenesis and offering unprecedented opportunities for better diagnostics, therapeutics and vaccines. Here, we provide a snapshot of the evolution of systems virology, from global gene expression profiling and signatures of disease outcome, to geometry-based computational methods that promise to yield novel therapeutic targets, personalized medicine and adeeper understanding of how viruses cause disease. To realize these goals, pipets and petri dishes need to join forces with the powers of mathematics and computational biology.

Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis

“…We can expect some antiviral drugs to have greater efficacy or side effects based on genetic differences between individuals. The concept of host molecular profiling and personalized medicine to treat medical illnesses, including viral infections, will be a critical field in the future (Law, Korth et al, 2013). With the advent of induced pluripotent stem cells (iPSCs) and the generation of cardiomyocytes derived from iPSCs, the efficacy of antiviral compounds and CVB-induced viral myocarditis can be quantitatively assessed on patient-derived cardiomyocytes (Sharma, Marceau et al, 2014).…”

Unifying immunology with informatics and multiscale biology

“…Hypothesis-free evaluation of these states by transcriptional profiling can be used to identify relationships that may have been more difficult to identify or even completely missed using more targeted approaches. Transcriptional profiles of immune-system cells have been used to develop molecular signatures for autoimmunity 1–3 , to explore vaccine efficacy 4–7 , to distinguish various phases of infection 8–11 and to suggest new treatment options for patients with rheumatological disease 12 and lymphomas 12,13 .…”

Noncoding RNA Expression During Viral Infection: The Long and the Short of It

“…Pro-apoptotic protein BIM [27] miR-BHRF1 Promotes cell cycle progression and proliferation; inhibits apoptosis [28] miR-BHRF1-3 CXCL-11 [29] lncRNA EBER-1 (166 nt) and EBER-2 (172 nt) Promotes cellular proliferation and transformation; inhibits apoptosis [30] KHSV miRNA miR-K12-10a TWEAKER [31] miR-K12-1, 3 and 4-3p Targets CASP3 to regualte apoptosis [32] miR-K12-9-5p and miRK12-7-5p KSHV RTA [33,34] miR-K12-11 targets IKKε to modulate IFN signaling [35] miR-K12-1 IkB-alpha [36] miR-K12-1, miR-K12-6-5p, miR-K12-11 MAF [37] miR-K12-4-5p Targets Rbl2 to regualte global epigenetic reprogramming [38] miR-K12-9 (miR-K9) and miR-K5 IRAK1 and MYD88 [17] miR-K1, miR-K3-3p, miR-K6-3p, miR-K11 THBS1 [39] miR-K1 p21 [40] miR-K12-3, miR-K12-7 C/EBPbeta p20 (LIP) [41] [9] quantification of tens of thousands of transcripts and have been widely used to characterize transcriptomic responses of cells, animal models, and human patients to virus infection (reviewed in [55]). Accurate detection and quantification of miRNAs poses several challenges that include the lack of common sequences for their purification, the high sequence similarity among miRNA within the same family, and the presence of natural variants of miRNAs, called isomiRs, which result from post-transcriptional nucleotide additions or deletions to 3 0 and 5 0 ends of mature miRNAs (reviewed in [56]).…”