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Denner Virology Journal (2017) 14:171 DOI 10.1186/s12985-017-0836-z REVIEW Open Access The porcine virome and xenotransplantation Joachim Denner Abstract The composition of the porcine virome includes viruses that infect pig cells, ancient virus-derived elements including endogenous retroviruses inserted in the pig chromosomes, and bacteriophages that infect a broad array of bacteria that inhabit pigs. Viruses infecting pigs, among them viruses also infecting human cells, as well as porcine endogenous retroviruses (PERVs) are of importance when evaluating the virus safety of xenotransplantation. Bacteriophages associated with bacteria mainly in the gut are not relevant in this context. Xenotransplantation using pig cells, tissues or organs is under development in order to alleviate the shortage of human transplants. Here for the first time published data describing the viromes in different pigs and their relevance for the virus safety of xenotransplantation is analysed. In conclusion, the analysis of the porcine virome has resulted in numerous new viruses being described, although their impact on xenotransplantation is unclear. Most importantly, viruses with known or suspected zoonotic potential were often not detected by next generation sequencing, but were revealed by more sensitive methods. Keywords: Porcine viruses, Virome, Xenotransplantation, Porcine endogenous retroviruses, Porcine cytomegalovirus, Porcine circoviruses, Hepatitis E virus Background virome of pigs and its impact on xenotransplantation. Xenotransplantation is being developed to overcome the These studies on the pig virome are, like investigations shortage of human tissues and organs needed to treat into the virome of humans and other species, only at organ failure by allotransplantation. Pigs are the pre- their very early stages [4]. The development of metage- ferred species to be used as donor animals for a number nomics has revolutionised virus discovery, leading to the of reasons including the size of the animals, their similar identification of many new viruses. These studies will physiology, and the ease with which they can be genetic- generate an enormous amount of data concerning the ally modified and cloned. prevalence of porcine viruses although these will be diffi- Although there are still some hurdles that have to be cult to interpret, especially with regard to the virus overcome, such as immunological rejection, physio- safety of xenotransplantation. logical incompatibility and risk of transmission of por- cine microorganisms, recent achievements in breeding genetically modified pigs, in the development of new im- Xenotransplantation and public health munosuppressive regimens and in approaches to safety By March 3, 2017, 118,265 waiting list candidates were suggest that xenotransplantation may soon be intro- listed at UNOS (United network for organ sharing), duced in the clinic (for review see [1–3]). among them 98,149 for kidney transplantations. However, In the past, only a few porcine viruses with known or in 2016 only 19,061 kidney transplantations were per- suspected ability to infect human cells or to accelerate formed in the US, indicating the increasing gap between transplant rejection have been analysed within the con- supply and demand, and the figures for heart transplanta- text of xenotransplantation. Next generation sequencing tions were 3191 versus 3994 (https://www.unos.org/). or deep sequencing techniques and metagenomic ana- Xenotransplantation could help to overcome this short- lyses now give the opportunity to analyse the entire age. Another field where xenotransplantation may have an enormous impact on public health is the Correspondence: [email protected] treatment of diabetes. In 2012, 29.1 million Americans, Robert Koch Fellow, Robert Koch Institute, Nordufer, 20 Berlin, Germany or 9.3% of the population, had diabetes, among them © The Author(s). 2017 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. Denner Virology Journal (2017) 14:171 Page 2 of 7 approximately 1.25 million children and adults with Table 2 Main viruses in the faeces of healthy Chinese pigs [7] type 1 diabetes (http://www.diabetes.org/diabetes-basics/ Virus % Virus family statistics/). Although the treatment of diabetes type 1 Porcine bocavirus 7 Parvoviridae with insulin was quite successful in the past using pig Porcine epidemic diarrhea virus (PEDV) 7 Coronaviridae insulin and only recently recombinant human insulin, Sapovirus 17 Caliciviridae complications were often observed, mainly due to in- Picornaviridae sufficient compliance of the patients leading to limb Sapelovirus 17 amputation and blindness. The total cost of diagnosed Torovirus 7 Coronaviridae diabetes in the United States in 2012 was 245 billion Posavirus-1 17 Picornaviridae dollars, most of which was spent on the treatment of Porcine astrovirus 72 Astroviridae complications while expenditure for insulin was relatively Porcine enterovirus-9 86 Picornaviridae low. A biologically regulated system based on porcine islet Kobuvirus 90 Picornaviridae cells would help avoid these complications [5]. Xenotrans- plantation therefore has the potential to have an enor- mous impact on public health. prevalence rates revealed that all samples were co- The porcine virome infected with at least two different viruses and that, not- As described in the abstract, the pig virome is the total ably, co-infection with 11 different viruses was identified amount of viruses in and on the pig body and includes in one sample [7]. Detailed analyses of German sows also the endogenous retroviruses. Initial attempts to ana- showed that the pig faecal virome is highly variable and lyse the porcine virome were undertaken using samples its general composition is mainly dependent on the age of the gut or faeces. These studies were started to better of the pigs [11]. Kobuviruses were predominantly de- understand the reasons for neonatal porcine diarrhoea, a tected in 12 day-old piglets, bocaviruses and others in common problem worldwide that contributes to mor- 54 day-old piglets and circoviruses in the sows [11, 12]. bidity and mortality among piglets [6]. Although investi- Viral metagenomics analysis in healthy and pigs suffer- gations of the porcine intestinal virome are so far ing from the postweaning multisystemic wasting syn- limited [7–9], samples from the distal jejunum of 19 drome (PMWS) showed that pigs have a considerable healthy pigs in a Swedish conventional herd yielded viral flora consisting mainly of small single-stranded and eight different viral families (Table 1). The most com- circular DNA viruses [13]. Although many viruses were mon were picornaviruses, followed by circoviruses [10]. also detected in the healthy pigs, the number of porcine Viral infections were already observed 24 to 48 h after circovirus 2 (PCV2) had increased considerably in the birth, indicating infection immediately post-partum, or PMWS pigs. alternatively, transplacental infection. Similar results were obtained when Chinese pigs were analysed [7] where, in addition to the viruses identified in Sweden, Table 3 Main viruses in the faeces of diarrhoeic Chinese pigs [7] the coronaviruses transmissible gastroenteritis virus Virus % Virus family (TGEV) and porcine epidemic diarrhoea virus (PEDV) Porcine bocavirus-2 59 Parvoviridae were found (Tables 2 and 3). In this study, the virus Porcine bocavirus-4 18 Parvoviridae Torque teno sus virus-2 (TTSuV-2) 7 Anelloviridae Coronaviridae Table 1 Main virus families of the pig virome [10] Porcine epidemic diarrhea virus (PEDV) 70 ? Virus family Characterisationa Prevalence in Prevalence in Swedish Porcine stool associated circular virus (PoSCV) 7 healthy pigs diarrhoeic pigs Po-circo-like 11 ? (%, n = 19) (%, n = 10) Sapovirus 33 Caliciviridae Adenoviridae dsDNA 16 0 Sapelovirus 48 Picornaviridae Anelloviridae ssDNA 5 10 Torovirus 33 Coronaviridae Astroviridae ssRNA 5 0 Posavirus-1 40 Picornaviridae Caliciviridae ssRNA 5 0 Porcine astrovirus 74 Astroviridae Circoviridae ssDNA 42 10 Coronavirus 7 Coronaviridae Parvoviridae ssDNA 11 0 Porcine enterovirus-9 85 Picornaviridae Picornaviridae ssRNA 53 40 Picobirnavirus (PBV) 15 Picobirnaviridae Reoviridae dsRNA 11 20 Kobuvirus 44 Picornaviridae ass single stranded, ds double stranded Denner Virology Journal (2017) 14:171 Page 3 of 7 When pig mucus (the raw material for production of were found in 42% of the individuals with a copy num- heparin) was investigated, parvoviruses (76%, within this ber of two to millions per 100,000 cells. Herpesviruses group bocaviruses represent 80%), circoviruses (16%) (altogether 41.6%) and anelloviruses (8.91%) were the and picornaviruses (2.5%) were mainly found [14]. most common viruses (Table 4). Among the viruses were Viruses known to be transmissible to humans such as numerous potentially pathogenic viruses such as Merkel influenza virus, hepatitis E virus (HEV) and encephalo- cell polyomavirus (MCPV), human immunodeficiency myocarditis virus (ECMV) [15, 16] were not found. virus
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  • Virus–Host Interactions and Their Roles in Coral Reef Health and Disease

    Virus–Host Interactions and Their Roles in Coral Reef Health and Disease

    !"#$"%& Virus–host interactions and their roles in coral reef health and disease Rebecca Vega Thurber1, Jérôme P. Payet1,2, Andrew R. Thurber1,2 and Adrienne M. S. Correa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cycling. Last, we outline how marine viruses are an integral part of the reef system and suggest $4&$($4-(01.,/-1'-(+.(80%/#-#(+1(%--.(./1'$0+1(0#(&1(-##-1$0&,('+>3+1-1$(+.($4-#-(:,+"&,,9( 0>3+%$&1$(-180%+1>-1$#; To p - d ow n e f f e c t s Viruses infect all cellular life, including bacteria and evidence that macroorganisms play important parts in The ecological concept that eukaryotes, and contain ~200 megatonnes of carbon the dynamics of viroplankton; for example, sponges can organismal growth and globally1 — thus, they are integral parts of marine eco- filter and consume viruses6,7.