Ebert et al. Virology Journal (2019) 16:109 https://doi.org/10.1186/s12985-019-1217-6 MEETINGREPORT Open Access Virology Downunder, a meeting commentary from the 2019 Lorne Infection and Immunity Conference, Australia Gregor Ebert1,4, Prasad N. Paradkar2 and Sarah L. Londrigan3* Abstract The aim of this article is to summarise the virology content presented at the 9th Lorne Infection and Immunity Conference, Australia, in February 2019. The broad program included virology as a key theme, and the commentary herein highlights several key virology presentations at the meeting. Keywords: Infection, Immunity, Inflammation, Pathogenesis Main text MERS, Marburg and Ebola viruses [1], but remarkably The Lorne Infection and Immunity Conference is one of are able to live asymptomatically with otherwise poten- five scientific meetings held during each month of tially lethal viruses [2]. Wang and colleagues are inter- February in seaside town of Lorne, on the Great Ocean ested in understanding the underlying immune mediated Road in Victoria (Australia). The specific aim of the regulatory mechanisms that facilitate a highly effective meeting is to bring together basic, clinical and transla- balance between viral defense and tolerance in bats as tional researchers - those who examine microbes and viral hosts. their impact on the innate or adaptive immune response, During their evolutionary adaption to effective flight, researchers who study the mechanisms that regulate bats not only developed elevated levels of basal alertness immune responses, and those who apply this knowledge reflected in increased metabolic heart rate and body to preventing and treating infectious and inflammatory temperature, they also seem to have evolved a highly diseases. 2019 was the 9th Lorne Infection and Immun- adapted immune defense against viral infections [3]. Re- ity Conference, convened by Heidi Drummer (Burnet In- markably, bats have increased tolerance to viral infec- stitute, Melbourne, Australia) and Paul Hertzog tions by exhibiting higher basal levels of innate defence (Hudson Institute of Medical Research, Melbourne, regulators but also a dampened innate immune response Australia). The broad program included virology as a upon infection, substitutional to increased responsive- key theme, and the commentary herein highlights sev- ness to viral pathogens [4]. The bat innate immune re- eral key virology presentations at the meeting. sponse appears to be ‘pre-activated’ with higher basal The ‘Infection and Inflammation’ session of the meet- levels of type I interferon expression, in contrast to ing was opened with a well-received presentation by humans, who are very quick responders to viral infec- Linfa Wang (Duke-NUS Medical School, Singapore) en- tions, but require a lot more dampening of their im- titled ‘Holy immune balance, batman’, about the highly mune signals afterwards to get back to basal levels. adapted immune response of bats to viral infections. Current research also shows the absence of any AIM2 Bats have been characterized as an important reservoir mediated inflammasome activation [5], dampened of various zoonotic viruses including Nipah, SARS, NLRP3 mediated inflammasome activation [6] and dampened STING activation [7] in bats upon infection, which are all mediators of a robust type I interferon * Correspondence: [email protected] ’ 3Department of Microbiology and Immunology, University of Melbourne, at response. Overall, Wang et al. demonstrated that bats the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, response to stress in form of viral infections is more tar- Australia geted and thus potentially more effective by numerous Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Ebert et al. Virology Journal (2019) 16:109 Page 2 of 3 adaptions and modifications of the innate immune Carrera, working with researchers at the Monash system. University and the University of Melbourne. In ‘Viruses and their Hosts’ session, Vinod Sundaramoorthy In the ‘Pathogenesis and Prevention of Infection’ ses- (CSIRO-Australian Animal Health Laboratories) dis- sion, Rosa Coldbeck-Shackley working with Michael cussed a novel defence mechanism in neurons against Beard at the University of Adelaide, Australia, and also Rabies virus (RABV). RABV is a neurotropic virus, colleagues at the Hudson Institute, presented findings which causes tens of thousands of deaths every year, on the importance of interferon-epsilon (IFN-ɛ)inthe despite available vaccines [8]. Endemic dog rabies innate immune response to ZIKV infection. IFN-ɛ is a results in an ongoing risk to humans in many novel type I IFN, encoded within the type I IFN locus resource-limited countries, whereas rabies in wildlife in mice and humans, whose function has recently been is important in North America and Europe [9]. characterized [16]. Like other type I IFNs, it acts via Requirement for an uninterrupted vaccine cold chain IFN-α receptors 1 and 2, activating Interferon stimu- and the high cost of the immunoglobulin component lated genes (ISGs). However, IFN-ɛ is preferentially of rabies prophylaxis therapies substantiate the unmet expressed by epithelial cells of the female reproductive need for novel RABV-specific antivirals [10]. Further- tract in both mice and humans, and in contrast to viral more, the pathogenesis of RABV relating to viral rep- induced type I IFN expression, IFN-ɛ is hormonally lication in neurons is not fully understood [11]. regulated. Other than mosquito-borne transmission, Although most of the infection with RABV manifests ZIKV is also sexually transmitted [17]. This makes the as the ‘furious’ form, where virus silently spreads research presented by Coldbeck-Shackley significant, through the neuronal axon without any damage, in 20 and concurs with previous studies where IFN-ɛ–defi- % of cases it can cause axonal damage in peripheral cient mice were more susceptible to infection with neurons leading to paralysis [12]. Using a new in sexually transmitted pathogens [16]. Thus, IFN-ε ap- vitro microfluidics model for studying synaptically pears to be a potent antipathogen and immunoregula- connected neurons, Sudaramoorthy investigated the tory cytokine that may be important in combating pathogenesis of different strains of Rabies virus, show- sexually transmitted infections that represent a major ing distinct mechanisms at play in determining dis- global health and socioeconomic burden. ease outcomes for each strain. Future efforts to define Also in the ‘Pathogenesis and Prevention of Infection’ a key molecular determinant in the viral replication session, Allison Abendroth (University of Sydney) pre- pathway in neurons may provide a novel therapeutic sented ‘Disarming the killer: targeting of natural killer target. cells by varicella zoster virus’. Varicella zoster virus In 2015, an association between Zika virus (ZIKV) (VZV), is known to infect numerous immune cell types infection during pregnancy as a cause of microcephaly such as T-cells and dendritic cells [18]. Moreover, the and other congenital abnormalities in the developing virus is able to modulate and manipulate innate and fetus and newborn, was made [13]. As such, there has adaptive immune responses to infection to its replicative been a plethora of recent ZIKV research focused on un- benefit. VZV infection of dendritic cells dampens type I derstanding the pathogenesis of disease, as well as im- IFN responses [19] and leads to evasion of CD8 T cell munity to the virus and the development of vaccines and recognition via downregulation of MHC class I expres- effective therapeutics. Novel findings pertaining to all of sion [20]. In addition, VZV mediated delay in immune these areas were presented throughout the meeting. responses to infection facilitates establishment of initial Developments in understanding the structure of ZIKV primary infection and lifelong latency in neurons. particles was showcased by Shee-Mei Lok (Duke-NUS, Most recently, Abendroth and colleagues found that Singapore). Lok and colleagues have previously solved a VZV also productively infects natural killer (NK) cells thermally stable 3.7 Å resolution cryo-electron micros- and that NK cells effectively transmit infection to other copy structure of ZIKV [14], and were able to now show permissive cell types [21] . The group is now trying to high resolution structures of ZIKV at various stages of understand, how NK cells, a cell type that normally viral assembly. Specifically, the organisation of the enve- demonstrates very effective direct and indirect antiviral lope protein of the virus and changes during assembly capacity, is manipulated by VZV infection, leading to and maturation were presented. Previously, Lok’s lab has impaired cytotoxicity and cytokine responses upon infec- also published structures of mature and immature den- tion and facilitating infection and spread of the virus. gue virus,