Phocine Distemper virus

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Classification

Phocine distemper virus is a species of ssRNA negative-strand virus in the order Mononegavirales, family Paramyxoviridae, and genus Morbillivirus [14].

Introduction

Phocine distemper virus (PDV) is a pathogen of the Morbillivirus genus of viruses that infect a number of mammals [15]. PDV more specifically infects pinnipeds (seals, walruses, etc.) and has caused several epidemics in the last one hundred years. In 2002, an outbreak of PDV outbreak killed between 22 ,000 and 30, 000 harbour seals (40% of regional population), one of the largest recorded mass mortality event in marine mammals [18]. The virus structure (genome, protein makeup, etc.) has been characterized in the past fifty years, but the dynamics of PDV in the environment, its ecological significance and mode of action, is less clear [1]. Active investigation of the virus is crucial considering the impact PDV has had on pinniped populations across the globe [10].

Phylogenetic tree showing the relationships of morbilliviruses of different species. Reproduced from and attributed to Graham Beards at English Wikipedia

Genome structure

Members of the Morbillivirus genus all have a genome made up of single stranded RNA, non-segmented and negative sense. The genome of PDV is 15,700 nucleotides in length (within the range of most Morbillivirus) and has all of the same core genes as the other members of the genus coding for matrix proteins, nucleocapsid, phosphoproteins, fusion glycoproteins, hemagglutinin, and coding for the main part of the RNA-based RNA polymerase ([1]. There are two more proteins coded in the genome (C and V) that are not involved in virus structure but impact viral pathogenicity. Both proteins block interferon (a protein that inhibits viral replication) signaling pathways in host cells hindering their ability to induce immune responses, especially against viruses [16]. The variation in the gene sequence for hemagglutinin from other viral sequences is what has most commonly been used to distinguish PDV from other Morbillivirus [3].

Virus structure

Like other Morbillivirus, PDV is an enveloped virus of icosahedral (20 faced polyhedron) shape, measuring about 150–250 nm in length. This envelope carries two transmembrane proteins: hemagglutinin and fusion glycoprotein, both responsible for merging of the virion envelope with the cell membrane [10]. PDV also has a helical nucleocapsid, where the genomic RNA and associated proteins are housed [10].

Metabolic processes

PDV, like all viruses, lacks a metabolism of its own and cannot reproduce without a host. In order to infect host cells PDV relies on hemagglutinin and fusion glycoproteins to attach to the host cell’s membrane receptor [1]. The types of cells PDV can infect are determined by the interaction of the H (Hemagglutinin) and F (Fusion) glycoproteins with the host cell receptor CD150 [1]. PDV can infect and utilize the cellular machinery of a variety of cells including white blood cells, blood vessel cells, and neural cells due to the wide range of membrane receptors it can interact with [1].

Ecology

Infecting its pinniped hosts is the main ecological interaction of PDV, and as a result, PDV infection is a mechanism of population control for pinnipeds throughout the world [1]. PDV has been detected in the Atlantic, Pacific, the Bering Sea, and waters around New Zealand [1]. PDV, like other Morbillivirus, is spread through aerosolization or fluid transmission. This limits the movement of PDV to when its pinniped hosts are on land, for example during breeding season [4]. Groups of European grey seals have developed herd immunity from PDV by breeding in November [4]. Hypotheses about why this is effective concern the juveniles being approximately 6 months old when they are exposed and thus less susceptible than newborns [4]. This is supported by the behavior constated in the Canadian harbor seals that breed in April that have not developed immunity [1].

Pathology

PDV effects free-ranging pinnipeds (harbor, grey, harp and hooded seals) by infecting respiratory epithelial cells first, then epithelial and endothelial (cells that line blood vessels) cells in various organs and finally, neural cells [1]. Because leukocytes (white blood cells), epithelial, endothelial and neural cells are targeted, PDV infection causes fever, fluid, mucal, or pustulent eye and nasal discharges, conjunctivitis, coughing and inflammation of the cornea, eye in general, and nose [13]. It can also cause discoloration of the skin, labored breathing, pneumonia with, in severe cases, lung damage that alters buoyancy, swimming and diving [13]. Depression, lethargy, head tremors, convulsions and seizures have also been observed [13]. In addition, secondary pneumonia caused by bacteria (Bordetella bronchiseptica, Streptococcus spp. Clostridium spp., etc), parasites (Parafilaroides spp.), or viruses (Phocid herpesvirus 1, Influenza A virus) often follow the primary PDV pneumonia [1]. During pregnancy, PDV infection also leads to abortion [1].

Histopathology (the study of changes in tissues from disease) includes depletion of leukocytes in the spleen, the thymus (an organ involved in immunity located in the neck region of vertebrates), the gut-associated lymphoid tissue, and in peripheral lymph nodes, as well as neuronal and glial cell death in the cerebral cortex. In the respiratory tract, alveolar cells seep out into the surrounding areas [12].

The severity of the disease seems to increase with the age of the organism impacted: pneumonia comes with more severe emphysema and stronger diving impediments [11].

Current research

Researchers are looking into using the biochemical makeup of PDV to predict future outbreaks in marine mammals [9]. Along with prediction of outbreaks, efforts are being made to prevent them through vaccination of pinnipeds in the wild [1]. Researchers are also trying to determine why some species of pinnipeds are more susceptible to the virus than others [1]. Studies have mainly focused on evaluating infection of marine animals by viruses in the Morbillivirus genus through sero-surveys, which is testing of specimens for antibodies (against PDV in this case). This is used as a direct measure of the population's immunity. Another way PDV is being studied is through diagnostics of observed pathology, virology and molecular biology (15). The mechanism of entry of PDV into cells of the central nervous system, for example, is yet to be fully understood. The development of models will expand our current knowledge of the molecular mechanisms and how the virus interacts with different cell types. Such studies will allow the improvement of vaccines and increase the efficiency of protection of endangered species[1].

References

[1] [Duignan, P., Van Bressem, M., Baker, J., Barbieri, M., Colegrove, K., De Guise, S., … Wellehan, J. (2014). Phocine Distemper Virus: Current Knowledge and Future Directions. Viruses, 6(12), 5093-5134. doi:10.3390/v6125093]

[2] [Goldstein, T., Mazet, J. A., Gill, V. A., Doroff, A. M., Burek, K. A., & Hammond, J. A. (2009). Phocine Distemper Virus in Northern Sea Otters in the Pacific Ocean, Alaska, USA. Emerging Infectious Diseases, 15(6), 925-927. doi:10.3201/eid1506.090056]

[3] [Hammond, J. A. (2005). Identification and real-time PCR quantification of Phocine distemper virus from two colonies of Scottish grey seals in 2002. Journal of General Virology, 86(9), 2563-2567. doi:10.1099/vir.0.80962-0]

[4] [Harris, C. M., Travis, J. M., & Harwood, J. (2008). Evaluating the Influence of Epidemiological Parameters and Host Ecology on the Spread of Phocine Distemper Virus through Populations of Harbour Seals. PLoS ONE, 3(7), e2710. doi:10.1371/journal.pone.0002710]

[5] [Härkönen, T., Harding, K., Rasmussen, T. D., Teilmann, J., & Dietz, R. (2007). Age- and Sex-Specific Mortality Patterns in an Emerging Wildlife Epidemic: The Phocine Distemper in European Harbour Seals. PLoS ONE, 2(9), e887. doi:10.1371/journal.pone.0000887]

[6] [Ludes-Wehrmeister E., Dupke C., Harder T.C., Baumgärtner W., Haas L., Teilmann J., Dietz R., Jensen L.J. & Siebert U. (2016). Phocine distemper virus (PDV) seroprevalence as predictor for future outbreaks in harbour seals. Veterinary Microbiology 183: 43-49]

[7] [Pádraig J. Duignan, Jeremiah T. Saliki, David J. St. Aubin, James A. House, and Joseph R. Geraci (1994) Neutralizing antibodies to Phocine Distemper Virus in Atlantic Walruses (Odobenus rosmarus rosmarus) from Arctic Canada. Journal of Wildlife Diseases: January 1994, 30(1): 90-94.]

[8] [Saliki, J., Lehenbauer, T. (2001). Monoclonal antibody-based competitive enzyme-linked immunosorbent assay for detection of morbillivirus antibody in marine mammal sera. Journal of Clinical Microbiology, 39(5):1877-81. doi:10.1128/JCM.39.5.1877-1881.2001.]

[9] [Wohlsein, P., Müller, G., Haas, L., Siebert, U., Harder, T. C., & Baumgärtner, W. (2007). Antigenic characterization of phocine distemper virus causing mass mortality in 2002 and its relationship to other morbilliviruses. Archives of Virology, 152(8), 1559-1564. doi:10.1007/s00705-007-0970-9.]

[10] [Lvov, D.K., Shchelkanov, M.Y., Alkhovsky, S.A., Deryabin, P.G. 2015. Zoonotic Viruses in Northern Eurasia. Elsevier. Chapter 5 Order Mononegavirales: 77-106.]

[11] [Rijks J.M., Read F.L., Van de Bildt M.W., Van Bolhuis H.G., Martina B.E., Wagenaar J.A., van der Meulen K., Osterhaus A.D., Kuiken T. (2008). Quantitative analysis of the 2002 phocine distemper epidemic in the Netherlands. Vet. Pathol, 45:516–530. doi: 10.1354/vp.45-4-516.]

[12] [Schumacher U., Horny H.P., Heidemann G., Schultz W., Welsch U. (1990). Histopathological findings in harbour seals (Phoca vitulina) found dead on the German North sea coast. J. Comp. Pathol, 102:299–309. doi: 10.1016/S0021-9975(08)80019-9.]

[13] [Siebert U., Gulland F., Harder T., Janiaux T., Seibel H., Wohlsein P., Baumgartner W. (2010). Epizootics in Harbour Seals (Phoca vitulina): Clinical Aspects. NAMMCO Sci. Publ. 8:265–274.]

[14] [NCBI. Taxonomy Browser: Phocine Morbillivirus. Retrieved Oct. 19, 2018, from https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11240&lvl=3&lin=f&keep=1&srchmode=1&unlock]

[15] [Jo, W., Osterhaus, A. and Ludlow, M. (2018). Transmission of morbilliviruses within and among marine mammal species. Current Opinion in Virology, 28, pp.133-141.]

[16] [Chinnakannan, S.K., Nanda S.K., and Baron, M.D. (2013). Morbillivirus V Proteins Exhibit Multiple Mechanisms to Block Type 1 and Type 2 Interferon Signalling Pathways. PLoS ONE 8(2): e57063. doi:10.1371/journal.pone.0057063]

[17] [Müller G, Wohlsein P, Beineke A, Haas L, Greiser-Wilke I, Siebert U, et al. Phocine Distemper in German Seals, 2002. Emerg Infect Dis. 2004;10(4):723-725. https://dx.doi.org/10.3201/eid1004.030591]

[18] [Klepac, P., Pomeroy, L. W., Bjornstad, O. N., Kuiken, T., Osterhaus, A. D., & Rijks, J. M. (2009). Stage-structured transmission of phocine distemper virus in the Dutch 2002 outbreak. Proceedings of the Royal Society B: Biological Sciences, 276(1666), 2469-2476. doi:10.1098/rspb.2009.0175]

Edited by [Alexandra LUTHER, Marine OLIVE, Roberto NUNES, Tony PHAM], students of Jennifer Talbot for BI 311 General Microbiology, 2018, Boston University.