Herpesviridae Neoplasms

Three herpesviruses of salmonids have been reported to be oncogenic. Oncorhynchus masou virus (OMV) causes cutaneous carcinoma (Fig. 3.7) in coho salmon, chum salmon (Oncorhynchus keta), cherry salmon (Oncorhynchus masou) and rainbow trout (Kimura et al., 1981; Yoshimizu et al., 1987, 1988). This virus was originally isolated from apparently healthy cherry salmon, (Kimura et al., 1981). Yamame tumour virus (YTV) was first isolated from a neoplasm on the jaw of a cherry salmon (Sano et al., 1983), and coho salmon tumour virus (CSTV) was isolated from neoplasms on coho salmon (Sano, 1988). These three viruses are serologically related (Hedrick et al., 1987; Sano, 1988), and OMV and YTV are strains of Herpesvirus salmonis Type 2 (Eaton et al., 1991b). There is strong evidence that both OMV (Yoshimizu et al., 1987) and YTV (Sano et al., 1983) are oncogenic; virus was re-isolated from neoplasms of experimentally infected fish.

Neoplasms caused by OMV develop 120-270 days (depending on species) after experimental exposure and occur most commonly on the jaws but also on fins, cornea and operculum (Yoshimizu et al., 1987). These neoplasms are composed of epithelial cells with enlarged nuclei, and there was invasion of adjacent connective tissue (Yoshimizu et al., 1988). Two types of neoplasms develop in kidney: one resembles the cutaneous lesions, and the second type contains hyperplastic renal tubules and cells resembling smooth muscle. The similarity between the cutaneous and renal neoplasms suggests the possibility of metastasis, but further study is needed to confirm this. Other malignant characteristics of these lesions are invasion of connective tissue and rapid growth. Neoplasms caused by YTV also develop on the mouth (Sano et al., 1983) and somewhat resemble the oral neoplasms caused by OMV. In addition to neoplasms, OMV also causes a lethal, acute disease in young salmonids (Kimura et al., 1983).

Morrison et al., (1996) observed virions with the appearance of herpesvirus in papillomas and squamous cell carcinomas of rainbow smelt (Osmerus mordax). An earlier attempt to find virus in similar carcinomas from this species was unsuccessful (Herman, 1988). Although similar in gross appearance, these lesions of rainbow smelt had malignant features that distinguished them from hyperplastic lesions common on European smelt (Osmerus eperlanus). However, particles resembling herpesvirus have been observed also in hyperplastic lesions of both rainbow smelt (Herman et al., 1997) and European smelt (K. Anders and Möller, 1985).

Non-neoplastic herpesviral lesions

Although some authors have considered the epidermal masses described below to be neoplasms, these lesions are characterized by well-differentiated cells and have little or no change from the normal tissue arrangement. The interdigitation characteristic of papillomas is not typically present or is not distinctly different from that in normal skin. Note that lesions associated with pike herpesvirus (discussed below) are characterized by epidermal hypertrophy, and are therefore quite different from other fish diseases caused by herpesviruses.

Herpes Virus Salmon
Fig. 3.7. (a) Coho salmon with a carcinoma on the upper jaw. Oncorhynchus masou virus was isolated from this tumour. (b) Histological section of a carcinoma caused by OMV. Bar = 20 mm. (Photographs provided by Takahisa Kimura.)

A disease known as 'carp pox' is one of the oldest recognized diseases of fish (Smail and Munro, 1989). The virus that causes carp pox, Herpesvirus cyprini, has been isolated from ornamental carp (Sano et al., 1985a,b, 1991). Thickened areas of epidermis developed 5-6 months after carp were immersed in a solution containing the virus. The lesions sloughed spontaneously and then recurred 7.5 months later (Sano et al., 1991). The virus was re-isolated from the hyperplastic lesions, fulfilling Rivers' postulates. In situ hybridization was used to detect the viral genome in lesions and other tissues of fish with active infections, and after lesions had regressed the viral genome could still be detected in gills, cranial nerve ganglia, and spinal nerves (Sano et al., 1993).

The historically entrenched name 'carp pox' is a misnomer because the causative agent is not a poxvirus. Several other names have been used for this condition, including fish pox, cutaneous warts, epithelioma papulosum, hyperplastic epidermal disease, papillosum cyprini, plaque warty hyperplasia, and variola (Wolf, 1988). Cyprinids other than carp are affected, and some reports indicate that non-cyprinids, including zander (pikeperch) (Stizostedion [=Lucioperca] lucioperca) and European smelt are also susceptible (van Duijn, 1973). Epidermal growths on wels (sheatfish) (Silurus glanis) (Wolf, 1988) and spawning European smelt (K. Anders and Möller, 1985; Lee and Whitfield, 1992) are similar to carp pox. Virus-like particles that resemble herpesvirus are visible in hyperplastic lesions of wels and European smelt, but viruses have not been isolated.

In addition to nomenclatural problems posed by carp pox, the neoplastic nature of the lesions also needs additional consideration. Lesions associated with this disease have been considered non-neoplastic by some authors (Schlumberger and Lucke, 1948; Nigrelli, 1954) while other authors describe the lesions as papillomas (Sano et al., 1991). There may be a progression from early non-neoplastic lesions to papillomas, but this has not been adequately described.

Carp pox lesions are white plaques composed of hyperplastic epithelial cells, and the lesions tend to harden with age (Schäperclaus, 1991). There is typically minimal involvement by the dermis (McAllister et al., 1985; Sano et al., 1991). Epidermal cells generally appear differentiated, and some goblet cells are present. As with many viral diseases of fish skin, the masses are transient and often regress as water temperature increases (McAllister et al., 1985) or during other critical phases of the fish's life cycle (K. Anders, 1989). Sano et al. (1991) speculated that replication of the virus in the hyperplastic tissue was suppressed or enhanced depending on water temperature. Lymphocytes are probably an important factor related to regression of the lesions (Morita and Sano, 1990).

Walleye have four types of cutaneous masses that are difficult to distinguish based on macroscopic examination (Yamamoto et al., 1985b). One of these diseases resembles carp pox and is probably caused by a walleye herpesvirus, Herpesvirus vitreum (Kelly et al., 1983). This virus was isolated from hyperplastic epidermis that typically occurs during spawning season and then regresses. The lesions are flat, translucent masses with diameters up to several centimetres. Superficially these lesions resembled areas of thickened mucus without well-demarcated margins.

One type of cutaneous mass found on northern pike is caused by pike herpesvirus, esocid herpesvirus 1; the lesion consists of hypertrophied epithelial cells (Yamamoto et al., 1983). Enlarged cells are up to 150 mm in diameter and are interspersed with normal-sized epidermal cells. Lesions appear as flattened, bluish-white masses with a granular texture. Enlarged nuclei of the hypertrophied cells contain herpesvirus capsids measuring 100 nm in diameter. Northern pike can also have lymphocystis, another disease characterized by hypertrophied cells, but lesions caused by pike herpesvirus lack a hyaline capsule and have an epidermal location (Yamamoto et al., 1983).

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