Di Guardo, Giovanni

Giacominelli Stuffler, Roberto

Mazzariol, Sandro

English

MAZZARIOL, SANDRO

Archivio istituzionale della ricerca - Università di Padova

Original Citation:Commentary: SLAM- and Nectin-4-Independent Noncytolytic Spread of Canine Distemper Virus inAstrocytesPublisher:Published version:DOI:Terms of use:Open Access(Article begins on next page)This article is made available under terms and conditions applicable to Open Access Guidelines, as described athttp://www.unipd.it/download/file/fid/55401 (Italian only)Availability:This version is available at: 11577/3216331 since: 2016-12-09T07:14:24Z10.3389/fmicb.2016.02011Università degli Studi di PadovaPadua Research Archive - Institutional RepositoryGENERAL COMMENTARYpublished: 09 December 2016doi: 10.3389/fmicb.2016.02011Frontiers in Microbiology | www.frontiersin.org 1 December 2016 | Volume 7 | Article 2011Edited by:Yasuko Tsunetsugu Yokota,Tokyo University of Technology, JapanReviewed by:Makoto Takeda,National Institute of InfectiousDiseases, JapanShigeru Morikawa,National Institute of InfectiousDiseases, Japan*Correspondence:Giovanni Di Guardogdiguardo@unite.itSpecialty section:This article was submitted toVirology,a section of the journalFrontiers in MicrobiologyReceived: 25 September 2016Accepted: 30 November 2016Published: 09 December 2016Citation:Di Guardo G, Giacominelli-Stuffler Rand Mazzariol S (2016) Commentary:SLAM- and Nectin-4-IndependentNoncytolytic Spread of CanineDistemper Virus in Astrocytes.Front. Microbiol. 7:2011.doi: 10.3389/fmicb.2016.02011Commentary: SLAM- andNectin-4-Independent NoncytolyticSpread of Canine Distemper Virus inAstrocytesGiovanni Di Guardo 1*, Roberto Giacominelli-Stuffler 1 and Sandro Mazzariol 21 Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy, 2Department of Comparative Biomedicine and FoodHygiene, University of Padova, Padova, ItalyKeywords: Canine Distemper Virus, Cetacean morbillivirus, Measles Virus, brain, astrocytes, viralneuropathogenesis, comparative neuropathologyA commentary onSLAM- and Nectin-4-Independent Noncytolytic Spread of Canine Distemper Virus inAstrocytesby Alves, L., Khosravi, M., Avila, M., Ader-Ebert, N., Bringolf, F., Zurbriggen, A., et al. (2015). J. Virol.89, 5724–5733. doi: 10.1128/JVI.00004-15As in the case of the small subset (8–20 per 1 million) of Measles Virus (MeV)-infectedhumans developing a peculiar neurological disease condition known as “subacute sclerosingpanencephalitis” (SSPE) (Garg, 2008; Kweder et al., 2015), Canine Distemper Virus (CDV) mayalso give rise to a persistent, “brain-only” form of disease in dogs, known as “old dog encephalitis”(ODE) (Reuter and Schneider-Schaulies, 2010; Sato et al., 2012). Interestingly, peculiar formsof morbilliviral disease resembling those reported in MeV-infected patients and CDV-infecteddogs have been also described among Cetacean Morbillivirus (CeMV)-infected striped dolphins(Stenella coeruleoalba) after the two major morbilliviral epidemics occurred in 1990–92 and 2006–08 in the Western Mediterranean. In a similar manner to what seen in CDV-affected canines andMeV-affected humans, dolphins hit by this form of infection harbor morbilliviral genome and/orantigens exclusively in their brain parenchyma (Domingo et al., 1995; Di Guardo et al., 2013).Is this enough to conclude that the aforementioned cases of “brain-only,”Morbillivirus infectionin striped dolphins could/should be regarded as reliable, comparative neuropathology and viralneuropathogenesis models in relation to their canine and human “counterparts”?We don’t know, although “yes and no” seems to be the best possible answer at the moment,provided that the agent- and host-related factors and mechanisms driving CeMV colonizationand persistence inside the brain of chronically infected dolphins are unknown (Di Guardo et al.,2013; Di Guardo and Mazzariol, 2016). In this respect, Signaling Lymphocyte Activation Molecule(SLAM/CD150), the cell receptor involved in the well-documented lymphotropic behavior ofMorbillivirus genus members, is not expressed by neurons, similarly to nectin-4, another receptormolecule accounting for morbilliviral epitheliotropism (Sato et al., 2012). Nevertheless, it hasalso been suggested that nectin-4 expression could be related to CDV neurovirulence, withnectin-4-immunoreactive neurons of the canine brain representing a preferential virus target(Pratakpiriya et al., 2012). Worthy to be mentioned, the long-lasting persistence of CDV in thebrain tissue from ODE-affected dogs has been recently described as the result of a non-cytolytic,astrocyte-to-astrocyte viral spread through a putative, hitherto unknown glial cell receptor,different from SLAM and nectin-4, which has been provisionally termed “GliaR” (Alves et al.,2015). This is of special concern in relation to “canine demyelinating leukoencephalitis,” oneof the various disease conditions suffered by CDV-infected dogs, a peculiar feature of which isDi Guardo et al. Canine Distemper Virus in Astrocytesrepresented by the viral colonization of vimentin-positiveastrocytes, a population of immature and/or reactive astroglialcells that might support CDV persistence and spread within thebrain of chronically infected dogs (Lempp et al., 2014), thusallowing the virus to “escape” the host’s intrathecal immuneresponse (Alves et al., 2015). Anyway, it should be additionallyunderscored that, despite the well-documented propensity ofCDV to colonize the host’s central nervous system (CNS), thereare remarkable differences among the various CDV strainsin terms of neurovirulence, neurological disease phenotypesand CNS areas targeted by the virus, with the moleculardeterminants specifically accounting for such differences beinglargely unknown. For instance, the Snyder Hill CDV strain,differently from the aforementioned “canine demyelinatingleukoencephalitis” model (Lempp et al., 2014; Alves et al.,2015), is highly neurovirulent, being responsible for a rapidlyprogressive and lethal polioencephalitis (Summers et al., 1984).Notwithstanding the above, a very limited viral colonization ofastrocytes has been recently observed by us in the cerebral tissuefrom three striped dolphins stranded along the Italian coastline,all carrying a “brain-only” form of CeMV infection. Still ofinterest, a quite prominent astrogliosis and astrocytosis have beensimultaneously detected in the brains from these dolphins (DiGuardo et al., in press).The brain pathomorphological changes’ pattern(s) shouldnot be viewed, however, as the only “parameter” upon whichbuilding a comparison between human SSPE, canine ODE andthe “brain-only” forms of morbilliviral disease that are beingincreasingly reported among Mediterranean striped dolphins(as well as in dolphins from other geographical areas of ourPlanet) (Di Guardo and Mazzariol, 2016). As a matter of fact,the “wild type” MeV strains/genotypes causing human SSPEare known to harbor a number of mutations, more frequentlyinvolving the viral matrix protein (M) gene and, to a lesserextent, also the fusion protein (F) and the haemagglutinin (H)genes. Furthermore, an enhanced viral spread, associated witha compromised capability of MeV strains/genotypes to produceinfectious, cell-free viral particles, have been related to theaforementioned gene mutations (Garg, 2008; Moulin et al., 2011;Kweder et al., 2015).To our knowledge, studies of this kind have never beenperformed on striped dolphins affected by “brain-only”forms of CeMV infection. The same is true as far as nectin-4expression within the cetacean CNS is specifically concerned.Thanks to similar investigations, indeed, it could be assessed“whether” and to “which extent,” among others, stripeddolphins with “brain-only” forms of CeMV infection may beregarded as “models” for the comparative neuropathologyand viral neuropathogenesis study of human SSPE inMeV-infected patients, as well as of ODE in CDV-infecteddogs.AUTHOR CONTRIBUTIONSGDG wrote the first draft of the Commentary, that was criticallyrevised by RGS and SM. The original manuscript’s text/versionwas entirely agreed by the three authors. The same also applies tothe revised manuscript’s text.REFERENCESAlves, L., Khosravi, M., Avila, M., Ader-Ebert, N., Bringolf, F., Zurbriggen, A.,et al. (2015). SLAM- and nectin-4-independent noncytolytic spread of caninedistemper virus in astrocytes. J. Virol. 89, 5724–5733. doi: 10.1128/JVI.00004-15Di Guardo, G., Di Francesco, C. E., Eleni, C., Cocumelli, C., Scholl, F., Casalone,C., et al. (2013). Morbillivirus infection in cetaceans stranded along the Italiancoastline: pathological, immunohistochemical and biomolecular findings. Res.Vet. Sci. 94, 132–137. doi: 10.1016/j.rvsc.2012.07.030Di Guardo, G., Giacominelli-Stuﬄer, R., Baffoni, M., Pietroluongo, G., DiFrancesco, C. E., Dufrusine, B., et al. (in press). Localization of viral antigensand brain ultrastructural findings in striped dolphins (Stenella coeruleoalba)with “brain-only” Dolphin Morbillivirus infection. 34th ESVP and 27th ECVPAnnual Meetings, 7-10. September. 2016, Bologna, Italy. J. Comp. Pathol. 155.Di Guardo, G., and Mazzariol, S. (2016). Cetacean Morbillivirus-associated pathology: knowns and unknowns. Front. Microbiol. 7:112.doi: 10.3389/fmicb.2016.00112Domingo, M., Vilafranca, M., Visa, J., Prats, N., Trudgett, A., and Visser, I. (1995).Evidence for chronic Morbillivirus infection in the Mediterranean stripeddolphin (Stenella coeruleoalba). Vet. Microbiol. 44, 229–239.Garg, R. K. (2008). Subacute sclerosing panencephalitis. J. Neurol. 255, 1861–1871.doi: 10.1007/s00415-008-0032-6Kweder, H., Ainouze, M., Brunel, J., Gerlier, D., Manet, E., and Buckland, R.(2015). Measles virus: identification in the M protein primary sequence of apotential molecular marker for subacute sclerosing panencephalitis. Adv. Virol.2015:769837. doi: 10.1155/2015/769837Lempp, C., Spitzbarth, I., Puff, C., Cana, A., Kegler, K., Techangamsuwan, S., et al.(2014). New aspects of the pathogenesis of canine distemper leukoencephalitis.Viruses 6, 2571–2601. doi: 10.3390/v6072571Moulin, E., Beal, V., Jeantet, D., Horvat, B., Wild, T. F., and Waku-Kouomou, D.(2011). Molecular characterization of measles virus strains causing subacutesclerosing panencephalitis in France in 1977 and 2007. J. Med. Virol. 83,1614–1623. doi: 10.1002/jmv.22152Pratakpiriya, W., Seki, F., Otsuki, N., Sakai, K., Fukuhara, H., Katamoto,H., et al. (2012). Nectin4 is an epithelial cell receptor for caninedistemper virus and involved in neurovirulence. J. Virol. 86, 10207–10210.doi: 10.1128/JVI.00824-12Reuter, D., and Schneider-Schaulies, J. (2010). Measles virus infection ofthe CNS: human disease, animal models, and approaches to therapy.Med. Microbiol. Immunol. 199, 261–271. doi: 10.1007/s00430-010-0153-2Sato, H., Yoneda, M., Honda, T., and Kai, C. (2012). Morbillivirus receptorsand tropism: multiple pathways for infection. Front. Microbiol. 3:75.doi: 10.3389/fmicb.2012.00075Summers, B. A., Greisen, H. A., and Appel, M. J. (1984). Canine distemperencephalomyelitis: variation with virus strain. J. Comp. Pathol. 94, 65–75.Conflict of Interest Statement: The authors declare that the research wasconducted in the absence of any commercial or financial relationships that couldbe construed as a potential conflict of interest.Copyright © 2016 Di Guardo, Giacominelli-Stuﬄer and Mazzariol. This is an open-access article distributed under the terms of the Creative Commons AttributionLicense (CC BY). The use, distribution or reproduction in other forums is permitted,provided the original author(s) or licensor are credited and that the originalpublication in this journal is cited, in accordance with accepted academic practice.No use, distribution or reproduction is permitted which does not comply with theseterms.Frontiers in Microbiology | www.frontiersin.org 2 December 2016 | Volume 7 | Article 2011

Commentary: SLAM- and Nectin-4-Independent Noncytolytic Spread of Canine Distemper Virus in Astrocytes

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Commentary: SLAM- and Nectin-4-Independent Noncytolytic Spread of Canine Distemper Virus in Astrocytes

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