Lymphocystis in Marine and Freshwater Fishes

Katie M. Kurkjian, DVM; Kenneth S. Latimer, DVM, PhD; and Pauline M. Rakich, DVM, PhD

Class of 2003 (Kurkjian), Department of Pathology (Latimer), and Athens Veterinary Diagnostic Laboratory (Rakich), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388

Introduction

Lymphocystis (lymphocystis disease, lymphocystis virus infection) is a chronic, self-limiting, viral disease affecting up to 125 species of teleosts worldwide. Freshwater, estuarine, and marine fish in warm-water, cool-water, and cold-water environments are susceptible to this disease. In general, lymphocystis is a disease of more evolutionarily advanced species of teleosts, such as herrings, perches, basses, flounders, snappers, and damselfishes. Because of viral replication and subsequent inhibition of mitosis in the host’s connective tissue cells, affected individuals develop macroscopic, nodular lesions that somewhat resemble warts. The greatly hypertrophied cells, called lymphocysts, typically occur on the skin or fins. Rarely, these lesions may develop in internal organs.

In 1874, J. Lowe documented the first case of lymphocystis in European flounder. Since then, scientists have performed considerable research on this disease, its host range, and repercussions of infection.

Significance

The study of fish diseases is of major importance for several reasons. Many fish populations have declined drastically over the last several decades. Scientists are attempting to discern the cause of these declines to prevent more fish from dying. Environmental pollution appears to be playing a large role in the development and / or exacerbation of disease. By understanding fish with respect to health and disease, fish populations can be used as sentinels to monitor water quality, to evaluate human impact on the environment, and to serve as harbingers of changes in human health.

Incidence of Lymphocystis

Lymphocystis is the most common viral infection of aquarium fish. Although lymphocystis disease has a low mortality rate, it may leave an individual disfigured. This disfigurement can have several consequences. If the gills are affected, the fish can have difficulty breathing. If the lesion is located around the mouth, the fish may have difficulty in feeding or may be unable to feed. Also, infected fish in confined environments or in the wild may be more likely to be targets of aggression or cannibalization. In addition, lymphocystis may be complicated by secondary bacterial or mycotic infections.

Lymphocystivirus

The etiological agent of lymphocystis disease is an iridovirus called lymphocystivirus. The genus name Iridovirus comes from Iris, the Greek goddess of the rainbow. In cases of heavy infection with some iridoviruses, affected individuals may have a "rainbow-like" iridescence. The four viruses comprising the Iridoviridae family are summarized in Table 1.

Iridoviruses are large (120-300 nm diameter), double-stranded, DNA viruses that replicate in the cytoplasm of infected cells (Fig. 1). Iridoviruses consist of an icosohedral or 20-sided capsid, an intermediate lipid layer, and a core composed of a linear, double-stranded DNA. Some iridoviruses may contain an outer envelope. These viruses have a wide host range and variable degree of pathogenicity. Iridoviruses have been isolated from non-mammalian vertebrate and invertebrate hosts that usually live in aquatic or moist habitats.

Figure 1. Transmission electron micrograph of infected dermal fibroblast containing iridovirus particles with characteristic hexagonal symmetry.

Thus far, 2 strains of the lymphocystivirus have been described based on DNA and polypeptide evaluation. LCDV-1 occurs in fish species such as flounder (Platichthys flesus) and plaice (Pleuronectes platessa), while LCDV-2 occurs in dabs (Limanda limanda). In addition to being terminally redundant (having duplicated copies of some genes), the DNA structure of both viral strains is linear but circularly permuted. Circular permutation means that the ends of each of the packaged DNA genomes differs from one virus particle to the next. Both of these characteristics are unique to iridoviruses and suggest that these viruses are evolutionarily adapted to be flexible to environmental pressure.

Host Range

The host range of lymphocystivirus includes over 125 species of freshwater and marine fishes belonging to 34 families and 9 orders. These fishes are susceptible to lymphocystivirus infection regardless of the temperature or salinity of the water in which they live or their geographical location. Susceptible species include freshwater fishes such as killifishes, basses, sunfishes, perches, and crappie as well as brackish water and marine fishes such as herrings, smelts, batfishes, scorpion fishes, sea basses, snappers, drums, goatfishes, scats, butterfly fishes, cichlids, damselfishes, wrasses, gobies, rabbitfishes, flounders, and porcupine fishes.

Transmission

Lymphocystis is transmitted by direct contact with infected individuals. In aquaria, resident fishes are infected most commonly via the introduction of new infected fish or exposure to fish products that are contaminated with the virus. Trauma to the skin via handling or netting, mating, parasitism, and aggressive behavior accelerates viral transmission among fish. Increased water temperature and stocking density also may facilitate the development of lymphocystis.

Clinical Signs

In general, the lymphocystivirus prefers to replicate in dermal fibroblasts, resulting in hypertrophied cells. Grossly, lesions affecting the skin and fins consist of masses of individual nodules that range from 0.3mm to >2.0 mm in diameter. Rarely, viral infection may produce nodular lesions involving the spleen and gastrointestinal tract. An ocular form of the disease also has been described in which the choroid, iris, and optic nerve are infected. In one instance, both ocular and splenic lesions were observed in a white crappie.

Viral-induced nodules are typically cream, pink, or gray in color, depending on the site of infection and degree of vascularity. Grossly visible lesions can develop from 1 week to >1 year following introduction of the virus. In the early stages of the disease or in mild viral infections, the skin lesions resemble a salt-like dusting of the body. These areas remain as discrete lesions or can coalesce into larger masses (Fig. 2). Nodules usually heal spontaneously, leaving little evidence of scar tissue.

Figure 2. Queen angelfish (Holacanthus ciliaris) infected with lymphocystis. A large pedunculated perioral mass is present that prevents normal feeding..

Pathology

Fibroblasts that are infected with lymphocystivirus continually enlarge or hypertrophy but do not undergo mitosis. During hypertrophy, the nucleus undergoes degenerative changes leading to condensation and fragmentation. The nucleoli become distorted and indistinct. The cytoplasm also changes, developing basophilic, intracytoplasmic inclusion bodies that appear as lacy, web-like fragments (plaice type) or dense vacuolated bodies (mullet type). In addition, a thick hyaline capsule surrounds the hypertrophied fibroblast or lymphocyst. This capsule may be an attempt to contain mild inflammation during early viral infection. However, the lymphocysts rupture in the later stages of infection, inciting a more intense inflammatory reaction.

Diagnosis by Cytology and Histopathology

Cytology wet mounts or touch imprints of skin and fin lesions usually are adequate for a presumptive diagnosis of lymphocystis. The lymphocysts appear as large, round, hypertrophied cells that are surrounded by a thick, smooth capsule (Fig. 3).

Figure 3. Wet mount of fin lesion from a fish with lymphocystivirus infection. Hyertrophied fibroblasts are surrounded by a thick, smooth capsule (new methylene blue stain).

Skin or fin biopsies submitted for histopathology provide a definitive diagnosis of lymphocytsis. The hypertrophied dermal fibroblasts or lymphocysts may aggregate to form masses (Fig. 4 and 5). The lymphocyts (infected fibroblasts) have irregular, basophilic, intracytoplasmic inclusion bodies and are surrounded by a smooth, eosinophilic capsule.

Figure 4. Skin biopsy from a fish with lymphocystis. The mass is composed of aggregates of spherical lymphocysts that are surrounded by a thick, hyaline capsule (10 x magnification, hematoxylin and eosin stain).	Figure 5. Higher magnification of skin biopsy showing lymphocysts with irregular, basophilic, intracytoplasmic inclusions and a smooth, eosinophilic capsule (45x magnification, hematoxylin and eosin stain).

Treatment and Control

Unfortunately, a specific treatment for lymphocystis is not available. Affected fish should be isolated and monitored for secondary bacterial or mycotic infections that should be treated with appropriate drugs. Lesions associated with lymphocystis eventually regress. In some individuals, tumorous lesions may require surgical debulking, particularly when they interfere with prehension (Fig. 6).

Figure 6. Queen angelfish (Holacanthus ciliaris) following surgical debulking of perioral tumorous mass due to lyphocytstis. This fish was able to feed more normally after surgery.

Fish should remain quarantined for at least 1 month after recovery. It is unknown whether previous infection with lymphocystivirus is protective against reinfection; however, recrudescence of viral infection has been reported in stressed fishes. Therefore, stress and skin trauma should be minimized. In addition, decreased stocking density and water temperatures may aid in disease suppression by decreasing stress.

Differential Diagnoses

Several other diseases may resemble lymphocystis. Cytology and histopathology are useful in the definitive diagnosis of each of these diseases.

Epitheliocystis (mucophilosis): Epitheliocystis is caused by a coccoid to coccobacillary organism. Lesions appear as small, 20 to 400 µm diameter, white nodules on the gills. Histologically, the hypertrophied chloride or goblet cells have granular, basophilic cytoplasm filled with coccoid or coccobacillary bodies. The nucleus, if present, is displaced to the periphery.

Ichthyophthirius multifilis (Ich or white spot disease): This disease is commonly observed and is due to protozoal parasitic infection. Lesions appear as small white spots on the skin, fins, tail, and gills. Cytologically, the parasite is large and round with a ciliated plasma membrane and a distinct macronucleus.

Walleye dermal sarcoma: This is a neoplasm composed of spindle cells that can be diagnosed by histopathology.

Idiopathic epidermal hyperplasia: This is a rare but benign disease characterized by variably-sized, white to pink, raised, cutaneous lesions. Histopathology reveals an irregularly thickened epidermis.

References

Bremont J, Bernard M: Molecular biology of fish viruses: A review. Vet Res 26:341-351, 1995.

Flugel RM: Lymphocystis disease virus. Current Topics Microbiol Immunol 116:133-150, 1985.

Huizinga HW: Surface and visceral lymphocystis disease in a white crappie, Pomoxis annularis. J Wildlife Dis 9:349-351, 1973.

Leibovitz L: Lymphocystis disease. J Am Vet Med Assoc 176:202, 1980.

Noga EJ: Fish Disease: Diagnosis and Treatment. St. Louis, Mosby-Year Book, Inc., 1996.

Stoskopf M: Fish Medicine. Philadelphia, W. B. Saunders Company, 1993.

Pilcher KS, Fryer JL: The viral diseases of fish: A review through 1978. Part 1: Diseases of proven etiology. CRC Crit Rev Microbiol 7:287-363, 1980.

Website: Microbiology and Immunology: BS335: Iridoviruses. http://www-micro.msb.le.ac.uk/335/kalmakoff/Iridoviruses.html.

Acknowledgement

Bolca Pesciara image courtesy of Pangaea Fossils. A rare and unusual fossil fish from the Eocene of Monte Bolca, this pycnodontiform holostean fish is from the family Pycnodontidae. The genus died out in the Eocene.

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