Future VIROLOGY Abstract Book Editor in Chief: Mark A Wainberg, McGill AIDS Centre, Canada

Although this is a time of unequalled advancement in global health, recent years have seen viral outbreaks of unprecedented scale, severity and complexity. Ebola and zika virus, as well as Middle East respiratory syndrome coronavirus (MERS-CoV) and yellow fever outbreaks highlight the need to move swiftly in the event of a new disease outbreak. Furthermore, the development of drug-resistant mutants is adding additional burdens to the already time-constrained virology community. Future Virology is a peer-reviewed journal that delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this ever-expanding area of research. It is an interdisciplinary forum for all scientists working in the field today. This document includes a summary of some recent top articles, all INDEXING of which are free to read in full on the journal’s website (http:// • Biobase, CAPCAS www.futuremedicine.com/loi/ • Chemical Abstracts fvl). For more information, to ask • Current Awareness in Biological Sciences a question, or to submit an article (CABS) proposal, please e-mail the journal’s • EMBASE/Excerpta Medica Commissioning Editor Frances IMPACT FACTOR • EMBiology Adlam (f.adlam@futuremedicine. com). • Journal Citations Report/Science Edition 0.886 • Science Citation Index Expanded (SciSearch) (2015) • Scopus®

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01 The worldwide emergence of ‘superbugs’ and a dry antibiotic pipeline threaten modern society with a return to the preantibiotic era. Phages – the viruses of bacteria – could help fight antibiotic-resistant bacteria. Review Phage therapy was first attempted in 1919 by Felix d’Herelle and Introducing yesterday’s phage therapy in was commercially developed in the 1930s before being replaced by today’s medicine antibiotics in most of the western world. The current antibiotic crisis fueled a worldwide renaissance of phage therapy. The inherent potential *1 1 1 Jean-Paul Pirnay , Gilbert Verbeken , Thomas Rose , of phages as natural biological bacterium controllers can only be put to Serge Jennes2, Martin Zizi3,4, Isabelle Huys5,6, Rob Lavigne7, use if the potential of the coevolutionary aspect of the couplet phage– Maia Merabishvili1,8,9, Mario Vaneechoutte8, Angus Buckling10 & Daniel De Vos1 bacterium is fully acknowledged and understood, including potential 1Laboratory for Molecular & Cellular Technology, Burn Wound Centre, Queen Astrid negative consequences. We must learn from past mistakes and set up Military Hospital, Brussels, Belgium credible studies to gather the urgently required data with regard to 2Burn Wound Centre, Queen Astrid Military Hospital, Brussels, Belgium the efficacy of phage therapy and the evolutionary consequences of its 3 Well Being Department, Queen Astrid Military Hospital, Brussels, Belgium (unlimited) use. Unfortunately, our current pharmaceutical economic 4Department of Physiology, Free University Brussels, Brussels, Belgium model, implying costly and time-consuming medicinal product 5Department of Pharmaceutical & Pharmacological Sciences, Centre for Pharmaceutical Care & Pharmacoeconomics, KU Leuven, Leuven, Belgium development and marketing, and requiring strong intellectual property 6Center for Intellectual Property Rights, KU Leuven, Leuven, Belgium protection, is not compatible with traditional sustainable phage therapy. 7Laboratory of Gene Technology, KU Leuven, Leuven, Belgium A specific framework with realistic production and documentation 8Laboratory of Bacteriology Research, Faculty of Medicine & Health Sciences, Ghent requirements, which allows a timely (rapid) supply of safe, tailor-made, University, Ghent, Belgium natural bacteriophages to patients, should be developed. Ultimately, 9Eliava Institute of Bacteriophage, Microbiology, & Virology, Tbilisi, Georgia economic models should be radically reshaped to cater for more 10Biosciences, University of Exeter, Cornwall Campus, Penryn, UK sustainable approaches such as phage therapy. This is one of the biggest Future Virology 7(4), 379–390 (2012). challenges faced by modern medicine and society as a whole. www.futuremedicine.com/doi/full/10.2217/fvl.12.24

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Interview Editorial Interview with Bryan R Cullen Towards an effective genital herpes vaccine: Bryan R Cullen past lessons and future prospects Duke University Medical Center, Durham, NC, USA William P Halford Future Virology 9(4), 345–350 (2014). Montana State University, Department of Veterinary Molecular Biology, Bozeman, MT 59717, USA www.futuremedicine.com/doi/full/10.2217/fvl.14.17 Future Virology 2(1), 1–6 (2007). www.futuremedicine.com/doi/full/10.2217/17460794.2.1.1 Bryan R Cullen obtained a BSc in biochemistry from Warwick University (UK) and a MSc in virology from the University of In 2007, the most effective means to acquire life-long immunity to Birmingham (UK) before moving to the USA, where he obtained a genital herpes will be to engage in romantic activity with a partner PhD in microbiology from Rutgers University (NJ, USA). In 1987, who is infected with herpes simplex virus (HSV)-2. Three out of four he was recruited to Duke University Medical Center (NC, USA) as a people who acquire HSV-2 in this manner are blissfully unaware of Howard Hughes Medical Institute Investigator and Assistant Professor. the molecular hitchhikers that they will carry for life, hidden away in He currently holds a James B Duke Professorship in the Department neurons of their peripheral nervous system. Such persons derive a huge of Molecular Genetics and Microbiology, and serves as Director of the benefit from these molecular hitchhikers: life-long immunity from the Center for Virology at Duke. Bryan Cullen’s interests have historically disease of genital herpes. revolved around the use of viruses as genetic tools to understand aspects of the biology of the eukaryotic cell, focusing particularly on RNA sequence-mediated gene regulation. Currently, his laboratory is Usage: 1176 Free studying the biogenesis and function of miRNAs, in particular virus- encoded miRNAs, and also works on human factors that act as innate inhibitors of both retrovirus infection and retrotransposon mobility. 05 Bryan Cullen has published over 280 research papers and is on the editorial board of 11 prominent journals. Review Usage: 1340 Free Leveraging APOBEC3 proteins to alter the HIV mutation rate and combat AIDS Judd F Hultquist1 & Reuben S Harris2 03 1Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN 55455, USA 2Department of Biochemistry, Molecular Biology & Biophysics, Department of Genetics, Cell Biology & Development, Institute for Molecular Virology and Center Review for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA Antivirals: current state of the art Future Virology 4(6), 605–619 (2009). www.futuremedicine.com/doi/full/10.2217/fvl.09.59 Erik De Clercq Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium At least two human APOBEC3 proteins – APOBEC3F and APOBEC3G – are capable of inhibiting HIV-1 replication by mutation Future Virology 3(4), 393–405 (2008). of the viral cDNA. HIV-1 averts lethal restriction through its accessory www.futuremedicine.com/doi/full/10.2217/17460794.3.4.393 protein Vif, which targets these APOBEC3 proteins for proteasomal degradation. The life-or-death interaction between human APOBEC3 Most of the antiviral agents that have been approved, and are proteins and HIV-1 Vif has stimulated much interest in developing currently used in the treatment of virus infections, are targeted at novel therapeutics aimed at altering the deaminase activity of the HIV, HBV, herpes simplex virus (HSV), varicella-zoster virus (VZV), APOBEC3s, thus changing the virus’ mutation rate to either lethal cytomegalovirus (CMV) and HCV or influenza virus. Additional or suboptimal levels. The current state of mechanistic information compounds for HIV, HBV, HSV, VZV, CMV, HCV, influenza virus is reviewed and the possible risks and benefits of increasing (via and several other viral infections, for example poxvirus (e.g., variola, hypermutation) or decreasing (via hypomutation) the HIV-1 mutation vaccinia and monkeypox), respiratory syncytial virus, hemorrhagic fever rate through APOBEC3 proteins are discussed. virus (e.g., Lassa, Rift Valley and Ebola) and enterovirus (e.g., polio, Coxsackie and echo), are still in the experimental stage, that is, under clinical or preclinical development. Usage: 1030 Free

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06 Among all the disease-causing agents in humans, viruses are the most notorious, active and important. Viruses are obligate parasites having DNA or RNA as their genetic material with markedly different Editorial mutation rates that can be quantified. Some viruses show remarkable Are adenoviral vectors the future for genetic stability and others show variable rate of mutation. In the foot-and-mouth disease vaccines? last 30 years, several new viruses have been reported from all over the world and have caused major outbreaks. Meanwhile, we are struggling Artur Summerfield against viruses and lack foolproof antiviral therapies against them. It Institute of Virology & Immunoprophylaxis, Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland has helped to understand the genetic, molecular, structural as well as Future Virology 5(1), 1–3 (2010). functional diversity of viruses, the intricacy of viral multiplication, immune escape, association of host cell machinery for replication and www.futuremedicine.com/doi/full/10.2217/fvl.09.74 host immune response. Owing to such development, researchers were able to find out appropriate targets against viruses, and as a result many In this issue of Future Virology, Grubman et al. review the progress antiviral drugs have been developed. in development of their foot-and-mouth disease (FMD) vaccines based on the replication-deficient adenovirus (Ad) since the first report in 1999. This provides the opportunity to raise the question Usage: 773 Free on the advances over the previous 10 years for FMD vaccines, and how such a vector-based vaccine compares with currently available vaccines. Clearly, vaccines against FMD are of major importance in 08 endemic regions for controlling the disease; they are also important as emergency vaccines to limit the spread of outbreaks in FMD-free countries and, thus, providing ethically acceptable control methods. Editorial For vaccines to be useful, they must fulfill certain criteria, the most Re-emergence of the knotty chikungunya important being the following: virus: facts, fear or fiction • Efficacy in rapid induction of protective immunity following a single Shailendra K Saxena shot of vaccine (particularly important for emergency vaccination); Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500 007 (AP), India Future Virology 2(2), 121–126 (2007). • Efficient induction of long-lasting immunity (particularly important www.futuremedicine.com/doi/full/10.2217/17460794.2.2.121 in endemic areas); Recent large-scale outbreaks of fever caused by chikungunya virus • Compatibility with the differentiation of infected from vaccinated (CHIKV) infection in several parts of the world have confirmed the animal (DIVA) principle; re-emergence of this virus. Its vast and rapid spread is a warning for future preparedness against emerging viruses around the globe. There • Safety in production and application; is no specific medicine and vaccine against the infection, therefore it is important to assess the current status and unique features of the • Economically feasible. chikungunya infection.

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Editorial Review Advances in antiviral drug discovery and The role of macrophages in influenza A virus development: Part I: Advancements in infection antiviral drug discovery Marlynne Q Nicol1, Bernadette M Dutia1 Shailendra K Saxena1, Niraj Mishra1, Rakhi Saxena1 1The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, EH25 9RG, UK 1Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500 007 (AP), India Future Virology 9(9), 847–862 (2014). Future Virology 4(2), 101–107 (2009). www.futuremedicine.com/doi/full/10.2217/fvl.14.65 www.futuremedicine.com/doi/full/10.2217/17460794.4.2.101 The importance of macrophages in the control of infections has long The history of infectious diseases is as old as the human civilization, been documented, but macrophages have also been shown to contribute and need of protection against these infections always remains one of to severe influenza A virus infections. Macrophage function ranges the prime concerns. Infectious diseases are a leading cause of death, and from highly proinflammatory to wound healing and regulatory and a alone accounted for one-fourth to one-third of total deaths worldwide. picture of diverse subsets with considerable plasticity in function and

www.futuremedicine.com 3 Future Abstract Book VIROLOGY phenotype is emerging. Within the lung three subsets of macrophage last three decades, several viruses have emerged/re-emerged and created populations have been identified: resident alveolar macrophages, potential public health problems. By contrast, the development of interstitial macrophages and exudate-derived macrophages. Here science and technology has helped us to understand genetic, molecular, we review model systems and techniques for defining macrophage structural as well as functional diversity of viruses, the intricacy of viral function in vivo and discuss macrophage infection in vitro. The use multiplication and association of host-cell machinery with infection. of detailed phenotypic approaches and techniques to dissect the role The information obtained provided road for development of many of individual macrophage subsets in vivo promises rapid advances in antivirals, as well as novel therapeutic strategies/targets against viruses. this area of research. Figure 1 demonstrates the classification of antiviral therapeutics with examples of each group. Antiviral development is a process in which modeling and experiments unite and, therefore, involves various stages Usage: 693 Free as well as various techniques. Antiviral development approaches can be broadly divided into three levels: physiological, mechanistic and genetic. The physiological approaches attempt to identify antiviral 10 targets through studies in whole organisms since infections only manifest at the level of the organism. This is the most popular method for developing therapeutics. The mechanistic approaches attempt to Editorial identify antiviral targets by comparing the intracellular pathways that Advances in antiviral drug discovery and regulate biological responses in cell culture, model animals and patients. development: Part II: Advancements in However, variation in host response and complexity of interactions antiviral drug development during infection often limit the applicability of this approach for therapeutics. The genetic approaches involve the identification of 1 1 1 Shailendra K Saxena , Niraj Mishra , Rakhi Saxena potential antiviral targets by comparing the differential expression of 1 Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500 007 (AP), India genes and proteins in normal and abnormal physiological conditions. Future Virology 4(3), 209–215 (2009). This is the most recent, technically challenging approach, and it could www.futuremedicine.com/doi/full/10.2217/fvl.09.1 produce large numbers of potential antiviral targets.

In spite of advances in scientific, technological and cultural development, microbes still remain a powerful threat and continue to evade Usage: 644 Free treatment, causing disastrous infectious diseases worldwide. Within the

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