Simon Goodman

University of Leeds, Leeds, UK

16.1 Introduction

A mass mortality exceeding 23,000 harbour seals (Phoca vitulina) in the North Sea during 1988 led to a scramble to identify the causative agent, eventually pointing to a novel morbillivirus, closely related to but distinct from canine distemper virus (CDV) (Osterhaus and Vedder, 1988; Dietz et al., 1989a, 1989b; Cosby et al., 1988; Curran et al., 1990; Heidejorgensen et al., 1992). This previously unknown virus, subsequently named phocine distemper virus (PDV), has since been the focus of extensive research, providing an important model for emerging infectious diseases in marine systems (Hall et al., 2006). Since 1988 it has been recognized that morbilliviruses are important causes of infectious disease mortality in marine mammals around the world, with CDV and PDV epizootics occurring in a range of pinniped species (Osterhaus et al., 1989a, 1992; Kennedy, 1998; Barrett, 1999; Kennedy et al., 2000), including a second major PDV epizootic in European harbour seals that killed 30,000 animals in 2002 (Harkonen et al., 2006), and mortalities in cetaceans due to dolphin and porpoise morbillivirus (CMV, PMV) (Kennedy et al., 1992; Barrett et al., 1993) and sirenians (Duignan et al., 1995a). In this chapter, I briefly review the structure, genetics and biology of PDV.

16.2 Virus Structure, Diversity, Taxonomy and Molecular Interactions with Hosts

The phocine distemper virus particle has an envelope, and the helical nucleocapsid core contains a single-stranded, non-segmented negative-sense 15.6 kilobase pair RNA genome. The genome has six transcriptional units/genes, aligned with the structure observed for other morbilliviruses, and these are annotated as per the structural proteins in other congeneric viruses: 3′ – N gene (1683 base pairs), P gene (1644 base pairs), M gene (1683 base pairs), F gene (2206 base pairs), H gene (1952 base pairs), L gene (~8900 base pairs) – 5′ (Curran et al., 1990, 1992; Kovamees et al., 1991; Rima et al., 1992; Blixenkrone-Moller, 1993).

Eight proteins are encoded among the six genes: nucleoscapsid (N, 523 amino acids); phosphoprotein (P, 507 amino acids); matrix protein (M, 335 amino acids); fusion glycoprotein (F, 537 amino acids); haemagglutinin/neuraminidase glycoprotein (H, 607 amino acids); and large RNA-dependent polymerase (L, 2184 amino acids). The P gene of PDV additionally codes for two further distinct non-structural proteins, V (299 amino acids) and C (174 amino acids). Together the M, F and H proteins are associated with the viral envelope (Cosby et al., 1988; Curran et al., 1992; Rima et al., 1992; Blixenkrone-Moller, 1993).

More limited sequence data for the P gene exist for additional strains. Comparisons of sequences from harbour seal outbreaks, with isolates from harp seal (Phoca groenlandia; Gulf of St Lawrence 1991), hooded seal (Cystophora cristata; New Jersey, USA 1998) and sea otters (Alaska 2004–2008), place the 2006 Maine isolate with the 1988 North Sea strains, while the 2006 sea otter, 1991 harp seal and 1998 hooded seal isolates were identical to the P gene sequence of the 2002 North Sea PDV isolate (Goldstein et al., 2009; Earle et al., 2011). Overall this suggests the circulation of multiple closely related PDV strains in north Atlantic and Arctic pinnipeds. Within the overall phylogeny of morbilli and paramyxoviruses, all PDV strains are consistently placed as a monophyletic sister clade to CDV across all genes (McCarthy and Goodman, 2010); recent evidence points to bats as the origin of the CDV/PDV group (Drexler et al., 2012).

In common with other morbilliviruses, it is assumed that PDV uses the lymphocyte-associated receptor CD150 (also known as signal lymphocyte activation protein, SLAM) as a primary receptor and CD46 (membrane co-factor protein, MCP) as a secondary receptor (Tatsuo et al., 2001; Tatsuo and Yanagi, 2002). Recently McCarthy et al. (2011) confirmed expression of SLAM and CD46 in harbour seals. The known infection pathways for morbilliviruses also suggest potential interactions with Toll-like receptors, interferon gamma (IFNG), interleukin-4 (IL4), IL8, IL10 and the vitamin A receptor (RARa) (Hall et al., 2006; McCarthy et al., 2011). Experimental studies using CDV in ferret models suggests that the H protein is a key determinant of virus interactions with SLAM, and that variation in the H protein may influence tissue tropism (Seki et al., 2003; Vongpunsawad et al., 2004; von Messling et al., 2005). Molecular evolution studies of CDV isolates from non-dog carnivores indicate that variation at a small number of key H protein residues involved in binding to SLAM may drive CDV adaptation to new hosts (McCarthy et al., 2007). Nielsen et al. (2009) reported that two clusters of H amino acid residues, positions 526–529 and 547–548 and amino acid 552 that have been implicated in the CDV as playing a role in SLAM binding were highly conserved, possibly reflecting overlapping host ranges between PDV and CDV (von Messling et al., 2005).

16.3 Clinical and Pathological Impacts of PDV

For sea otters necropsied during the Alaskan mortality event, potential secondary bacterial infections of Streptococcus infantarius subsp. coli (S. bovis/equinus complex) causing alvular endocarditis and septicaemia in mature adults were reported in association with PDV infections, suggesting possible immunosuppressive effects similar to those seen in European harbour seals (Goldstein et al., 2009).

Antibodies and nucleic acid sequences for PDV have been detected in numerous species (see below), but without the high levels of mortality reported for European harbour seals. For example, serological evidence demonstrates widespread exposure of European grey seals (Halichoerus grypus) to PDV in 1988 and 2002, but there have been no substantiated cases of fatal PDV infections in adults of this species (Hall et al., 2006), suggesting that grey seals may act as asymptomatic carriers of the infection. Similarly, where evidence of PDV infection has been detected in other phocid seals, this is also in the absence of obvious mortality events. This suggests that there are substantial inter-species differences in PDV susceptibility and mortality, but the underlying genetic, environmental and epidemiological causes of these differences remain to be determined.

16.4 PDV Hosts and Global Distribution

After the first identification of PDV in European harbour seals following the 1988 epizootic, numerous surveys for morbilliviruses have been carried out in archived sera and tissue from pinnipeds and potential terrestrial hosts, together with now routine testing of stranded pinnipeds.

No direct evidence has been reported demonstrating the presence of PDV in European seals prior to 1988 (Osterhaus et al., 1988, 1989b; Harwood et al., 1989), although anecdotal historical accounts hint at harbour seals with symptoms consistent with PDV in the Orkneys during the 1930s (Harwood and Hall, 1990). Serological evidence for PDV neutralizing antibodies prior and subsequent to 1988 has been reported in archived sera from Arctic populations of grey seals (Carter et al., 1992; Henderson et al., 1992; Duignan et al., 1995b), harp seals (Dietz et al