Retroviridae Neoplasms

Retroviruses probably cause most infectious neoplasms of fish. These neoplasms are diverse and include lymphosarcoma or leukaemia, dermal sarcoma, fibroma, leiomyosarcoma, papilloma and neural neoplasms. Viruses causing these diseases are difficult to isolate in cell culture, but transmission of the disease by cell-free inoculum and presence of reverse transcriptase activity provide evidence that retroviruses are the aetiological agents causing certain neoplasms of fish. Virus-like particles, typically C-type particles, have been seen in some lesions thought to be caused by retroviruses, but this evidence must be interpreted cautiously because of the similar appearing neurosecretory granules in some cells (Harada et al., 1990).

Lymphosarcoma in northern pike (Esox lucius) and muskellunge (Esox masquinongy) is probably caused by a retrovirus. The neoplastic cells contain C-type particles and reverse transcriptase (Papas et al., 1976, 1977; Sonstegard,

1976), and neoplasms were transmitted by cell-free tumour homogenate (Mulcahy and O'Leary, 1970; Brown et al., 1975; Sonstegard, 1976). The most common lesions in this disease are large, infiltrating masses in skin and underlying muscle. Neoplastic cells resemble haemocytoblasts (Mulcahy et al., 1970) or lymphoblasts (Sonstegard, 1975), and they are present in blood. Metastases occur in kidney, spleen and liver (Sonstegard, 1975). Increased prevalence of this disease was reported in polluted waters (Brown et al., 1973,

1977), but studies in Ireland discounted the role of pollution (Mulcahy, 1976).

A plasmacytoid leukaemia of chinook salmon was transmitted with a cellfree filtrate (Kent and Dawe, 1993), and reverse transcriptase activity and viruslike particles were demonstrated (Eaton and Kent, 1992). In this neoplasm, proliferating cells, which appeared to be plasmablasts, infiltrated most organs. Anaemia and high mortality rate of chinook salmon in netpens were caused by this leukaemia (Kent et al., 1990), which also occurs in wild chinook salmon (Eaton et al., 1994).

Lymphosarcoma in medaka (Oryzias latipes) consisted of dermal masses of homogeneous blast cells infiltrating through muscle (Harada et al., 1990). The neoplasms spread directly to adjacent tissues, and also reached the thymus, spleen and kidney. C-type particles were in the neoplastic cells, but the similarity in appearance of these particles and neurosecretory granules complicates the conclusion that these particles are retroviruses.

Neurofibromas and malignant schwannomas of bicolour damselfish (Pomacentrus partitus) can be transmitted by injection of filtered (0.2 mm)

tumour homogenate (Schmale, 1995), and epizootiological evidence suggests that an infectious agent is transmitted horizontally to spread this disease (Schmale, 1991). A retrovirus was found in tumorigenic cell lines derived from fish with spontaneous or experimentally induced neurofibromatosis (Schmale et al., 1996). This disease is a potential model for human neurofibromatosis (Schmale and Hensley, 1988).

Sarcomas in fish are also caused by retroviruses. The best studied of these is dermal sarcoma of walleye (Stizostedion vitreum). This disease can be transmitted through intramuscular injection of fish with a cell-free filtrate of tumour homogenate (Bowser et al., 1990, 1996; Martineau et al., 1990a), and viral DNA can be detected in tumour-bearing and tumour-free walleye from an infected population (Poulet et al., 1996). Molecular characterization of virus from walleye dermal sarcoma indicates that the virus is distinctive from other retroviruses and has characteristics of some lentiviruses and spumaviruses (Martineau et al., 1992). These neoplasms are typically composed of fibroblast-like cells, but the tumours sometimes contain osteoid material and resemble osteosarcomas (Martineau et al., 1990b; Earnest-Koons et al., 1996). Cells are anaplastic, and in most cases are limited to the dermis with no indication of invasion or metastasis. However, locally invasive lesions can occur (Earnest-Koons et al., 1996). Viral particles are visible in some tumours (Walker, 1969) but are not seen in others (Martineau et al., 1990b). There are seasonal changes in prevalence of this disease, with lowest prevalence in summer (Bowser and Wooster, 1991), and infiltration by lymphocytes was associated with degeneration and necrosis in some neoplasms (Martineau et al., 1990b). Although the density of lymphocytes was not significantly related to season, immunological functions of these cells could be affected by temperature.

Retrovirus-like particles were observed in swimbladder leiomyosarcomas of Atlantic salmon (Salmo salar) reared in cages (Duncan, 1978). The neoplasms consisted of well differentiated, spindle-shaped cells with elongated cytoplasmic processes (McKnight, 1978). Collagen was barely detectable and mitoses were common.

Retrovirus-like particles were also observed in fibromas on the lips of freshwater angelfish (Pterophyllum scalare) from several sources (Francis-Floyd et al., 1993). These lesions were surgically removed and did not recur in 12 months. These viruses were not isolated nor experimentally transmitted, and their contribution to development of these neoplasms is uncertain.

One of the fish neoplasms thought to be caused by retroviruses may be a member of the subfamily Lentivirinae. A fibroma in hooknose (Agonus cataphractus) contained lentivirus-like particles that could be seen with electron microscopy (K. Anders et al., 1991). If these particles are viruses, this was the first report of a lentivirus in a fish. The lesions were located in the dermis, and were globular or flattened. One of seven neoplasms examined was invading adjacent muscle and was considered a possible fibrosarcoma. Two of the neoplasms were yellow and contained large numbers of inflammatory cells.

White suckers (Catostomus commersoni) from Burlington Harbour and Oakville Creek in western Lake Ontario, had prevalences of oral papillomas of 35.1% and 50.8%, respectively (Sonstegard, 1977). Electron microscopy revealed C-type particles in the papillomas, and reverse transcriptase activity was associated with particulate fractions separated on sucrose gradients. These papillomas were less common on fish from less polluted areas. Similar tumours were transmitted by injection of cell-free filtrate of papillomas (Premdas and Metcalfe, 1996), but virus-like particles were not seen in recent studies (Smith et al., 1989; Premdas and Metcalfe, 1996). Pathogenesis of neoplasms in fish from this area is complex, and their cause is uncertain (Hayes et al., 1990). Extract of sediment from another western Lake Ontario location, Hamilton Harbour, contains high levels of polycyclic aromatic hydrocarbons (PAH) and PCB, and 12 months after rainbow trout yolk-sac larvae were given a single injection of this sediment extract they had hepatic neoplasms (Metcalfe et al., 1990).

Atlantic salmon papillomas appear as white plaques or wart-like masses that are up to 4 cm in diameter and 2-5 mm thick (Carlisle and Roberts, 1977). The lesions occur on the posterior portion of the head (opercula), trunk, tail and fins, but not on the jaws and anterior portions of the head. Most cells in these papillomas are uniform in appearance, but some are anaplastic or pleomorphic, have bizarre mitotic figures, or form cords or whorls. The basement membrane is difficult or impossible to discern, but definite invasion through the basement membrane is not apparent. A sharp line of demarcation between the lesion and the normal epidermis is typical. Virus-like particles in cells had an outer, electron-dense coat and were 125-150 nm in diameter with a core 70-95 nm in diameter (Carlisle, 1977). This virus has not been isolated. This disease is seasonal with a peak in August, and sloughing of the papillomas may be related to the numerous inflammatory cells that invade the lesion (Carlisle and Roberts, 1977).

Neoplasms of hybrid Xiphophorus, which have been thoroughly studied by geneticists, contain virus-like particles, but the relation between viruses and these neoplasms is unknown. Particles resembling retroviruses were seen in neuroblastomas of fish injected with 5-bromodeoxyuridine; the neoplasms had been induced by MNU (Kollinger et al., 1979). A retrovirus was also found in a cell line established from melanomas of southern platyfish (Petry et al., 1992). Other virus-like particles that were not retroviruses were also seen in melanomas of Xiphophorus (Kollinger et al., 1979; Esaka et al., 1981).

Non-neoplastic retroviral lesions

Northern pike and walleye have hyperplastic epidermal lesions with C-type particles that are presumably retroviruses (Yamamoto et al., 1983, 1985a,b). The lesions are smooth, translucent masses with thickness up to 2 mm and variable diameter up to 20 mm. Within the masses are occasional pegs of dermal tissue, and there is generally a lack of goblet cell differentiation over most of the mass. Walleye epidermal hyperplastic lesions containing retrovirus tend to be more discrete and well demarcated than the hyperplastic lesions apparently caused by walleye herpesvirus. The minimal change in the relationship between the dermis and epidermis distinguishes these lesions from papillomas of other species. However, this disease has been considered as neoplastic by some authors (Wolf, 1988; Eaton and Kent, 1992).

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