Reunion of the Conjoined Twins Disciplines

EDITORIAL

Viral immunology: reunion of the conjoined twins disciplines

Chi-Chiang Yang1,2

Cellular & Molecular Immunology advance online publication, 4 January 2016; doi:10.1038/cmi.2015.94

It is generally accepted that the concept 1796, Edward Jenner (1749–1823) de- of the virus as a replicative organism dif- veloped the first smallpox vaccine to ferent from other microorganisms, and protect against viral infection,3 and his the scientific study of viruses and the work is widely regarded as the founda- infections they cause, began in the clos- tion of immunology despite the fact that ing years of the nineteenth century. In he was neither the first to suggest that 1884, Charles Chamberland (1851– infection with cowpox conferred specific 1931) invented a filter—known today immunity to smallpox nor the first to as the Chamberland filter—with pores attempt cowpox inoculation for this pur- smaller than the size of bacteria to com- pose. Moreover, at that time, he did not pletely remove bacteria from a solution.1 know the disease etiology and did not In 1892, Dmitry Ivanovsky (1864–1920) know that viruses existed. Some scien- used Chamberland filters to show that tists, however, would rather believe that leaf sap from a diseased tobacco plant this point in time was the beginning of a remained infectious to healthy tobacco new discipline known as virology. It is plants despite the filtration step.2 This therefore reasonable to consider these result is the first evidence of the existence two disciplines as conjoined twins that of viruses. Nevertheless, it was not until are closely related and were birthed at 1898 that Martinus Beijerinck (1851– the same time. 1931) repeated the experiments and Currently, viral immunology is a called the filtered infectious substance a rapidly growing field that has exclusively Chi-Chiang Yang ‘virus’ and not a ‘toxin’, and this discov- covered all aspects of human and animal infection often triggers a first-line host ery is considered to be the beginning viral immunology, including research defense through the production of type of the field of virology. However, the and development of viral vaccines, I IFN, which is a broadly acting antiviral definition of ‘virus’, an obligatory in- immunological characterization of viral cytokine, and other inflammatory cyto- tracellular parasite smaller than bacteria components, viral infection immunity, kines. These proteins induce an antiviral containing both nucleic acid and protein virus-based immunological diseases, state in the host cells, thereby interfering that replicates by assembly but not divi- immunopathogenic mechanisms, viral with viral replication. Wong and Chen sion, was established in the 1950s, less immunological diagnoses and methods, comprehensively outline what is cur- than 60 years ago. The realization that and immunology with tumor viruses. rently known regarding the signaling many plant and animal diseases can be The interactions between viruses and the hosts they infect are multifactorial. pathways involved in the production of attributed to this newly recognized type In this special issue of Cellular and type I IFN and IFN-stimulated genes of agent came even more recently. In Molecular Immunology, three invited (ISGs) and the tactics that HCV uses to 1Department of Clinical Laboratory, Chung Shan expert reviews presented the most recent subvert innate immunity. The effector Medical University Hospital, Taichung 40201 and advances in this field for the readers. In mechanisms of scaffold ISGs, which were 2 School of Medical Laboratory and Biotechnology, the first review, the complexity and func- identified from genome-wide siRNA Chung Shan Medical University, Taichung 40201. Email: [email protected] tionality of the pleiotropic interferon screens, known to modulate IFN func- Received 5 October 2015; Accepted 5 October (IFN) system in hepatitis C virus tion in HCV replication were summar- 2015 (HCV) infection were discussed.4 Viral ized. The elucidation of the specificity Editorial 2

and the mode of action of these emerging Finally, in the third review, the pro- tinuing threat to human health. In the ISGs is useful for the identification of tective immune responses elicited by past, we have achieved some notable suc- novel cellular targets against which effec- the vaccine against yellow fever virus cesses in the struggle against viruses, e.g., tive HCV therapeutics can be developed. were discussed to provide insights for the eradication of smallpox in the 1980s. Wong and Chen also discussed the func- the development of a protective dengue However, the success of smallpox erad- tions of several cellular determinants virus (DENV) vaccine.8 As many as 400 ication has made a large fraction of critical for regulating host immunity. million dengue infections occur every the population now susceptible to small- In the second review, Liu et al. year, of which 96 million manifest clin- pox, as mandatory smallpox vaccination reviewed the current literature on how ically as dengue fever.9,10 Coincidentally, was discontinued in the USA in the various effectors of the immune system during the preparation of this editorial, early 1970s. To counter the continuing initiate the cytokine storm and exacer- we found that Taiwanese records show threat posed by viruses, it is essential to bate pathological damage in hosts with more than 20 000 cases of dengue fever understand the body’s innate and ada- 5 severe influenza virus infection. The this year, which is the most in the coun- ptive immune responses against viral persistent outbreaks of influenza and try’s history for this time of year. The infection. avian influenza in recent years suggest outbreaks in other Southeast Asian coun- that influenza is a major threat to public tries, including Malaysia, Singapore, and health. In the event of a viral infection, Vietnam, have also been historically severe the severity of a disease is the result of the this year. The use of vaccines to prevent interplay between the viral virulence and viral infection is the most cost-effective 1 Teri Shors Understanding Viruses. Sudbury, MA: Jones & Bartlett Publishers, 2008: host immune resistance. Pro-inflammat- public health strategy. However, there are 76–77. ory cytokines or chemokines can lead to currently no vaccines to prevent infection 2 Sussman M, Topley WWC, Wilson GK, the recruitment of inflammatory cells. with dengue virus. Liang et al. closely Collier LH, Balows A. Topley & Wilson’s When the pathogen-associated molecu- examined the immunological factors that Microbiology and Microbial Infections. lar patterns from the virus are recognized have been associated with the protection London: Arnold, 1998: 3. 3 Baxby D. ‘‘Jenner, Edward (1749–1823)’’. by the pattern recognition receptors of conferred by the yellow fever virus (YF- Oxford Dictionary of National Biography. innate immune cells, the inflammatory 17D)vaccineinthehopeofestablishing Oxford University Press. Retrieved 14 response begins.6,7 Next, an increased a strategy for the development of an effi- February 2014. expression of inflammatory, antiviral, cacious DENV vaccine. The kinetics of 4 Wong MT, Chen SS-L. Emerging roles of interferon-stimulated genes in the innate and apoptotic genes occurs and is various types of the immune response, immune response to hepatitis C virus infec- accompanied by abundant immune cell including the efficient activation of APC, tion. Cell Mol Immunol 2015; 12:11–35. infiltration and tissue damage. As the the induction of potent innate immune 5 Liu Q, Zhou YH, Yang ZQ. The cytokine cytokine network is important for the responses, the production of pro-inflam- storm of severe influenza and development of immunomodulatory therapy. Cell Mol process of viral infection and can be matory cytokines, the eliciting of high Immunol 2015; 12: 3–10 potential targets for therapeutic interven- titers of neutralizing antibodies, the induc- 6 Medzhitov R. Recognition of micro- tion, it would be helpful to investigate the tion of poly-functional CD41 and CD81 organisms and activation of the immune efficacy of immunomodulatory therapy T cells, and the stimulation of long-term response. Nature 2007; 449: 819–826. 7 Barton GM. A calculated response: control in these infections. In this article, the cur- cellular memory and humoral immunity of inflammation by the innate immune rent immunomodulatory strategies for induced by the YD-17D vaccine were dis- system. J Clin Invest 2008; 118: 413–420. the treatment of cytokine storms in severe cussed in detail. Hopefully, a careful exam- 8 Liang HB, Lee M, Jin X, Guiding dengue influenza, including corticosteroids, per- ination of the immune responses to DENV vaccine development using knowledge gained from the success of the yellow fever oxisome proliferator-activated receptor infection, and a comparison of that with vaccine. Cell Mol Immunol 2015; 12: 36–46. agonists, sphingosine-1-phosphaterecep- the knowledge on YF infection and YF- 9 Bhatt S, Gething PW, Brady OJ, Messina JP, tor 1 agonists, cyclooxygenase-2 inhibitors, 17D vaccine-elicited protection, may help Farlow AW, Moyes CL et al. The global antioxidants, anti-TNF therapy, intrav- to establish a strategy for the development distribution and burden of dengue. Nature 2013; 496: 504–507. enous immunoglobulin therapy, statins, of a dengue vaccine. 10 Kramer LD, Ebel GD. Dynamics of flavivirus arbidol, herbs, and other potential thera- Virus infection can result in acute or infection in mosquitoes. Adv Virus Res peutic strategies were also reviewed. chronic disease, which represents a con- 2003; 60: 187–232.

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