key: cord-0037562-v3ylisbt
authors: Alroy, Joseph; Lyons, Jeremiah A.; Kavirayani, Anoop M.
title: Viral Pulmonary Disorders in Animals: Neoplastic and Nonneoplastic
date: 2013-08-26
journal: Viruses and the Lung
DOI: 10.1007/978-3-642-40605-8_24
sha: 68e351f6a8d6bc2b34edfc6ef03143f5ab42d6c2
doc_id: 37562
cord_uid: v3ylisbt

Respiratory infections in animal species are as ubiquitous as they are in humans. Species that may be affected include mammals, birds, and reptiles. In these animal species some viruses primarily infect the respiratory tract, while other viruses infect non-respiratory organs. Viruses are generally classified according to the type of their nucleic acid, their protein structure, and whether or not they have a lipid-containing envelope surrounding the viral particle. In general, most viruses gain entry into the lungs via the conducting airways. In nonprimate mammalians these infections are most prominent in the cranioventral lung lobes because of their horizontal position. Table 24.1 lists some of the major viruses that cause pneumonia and other lung diseases in animals.

Respiratory infections in animal species are as ubiquitous as they are in humans. Species that may be affected include mammals, birds, and reptiles. In these animal species some viruses primarily infect the respiratory tract, while other viruses infect non-respiratory organs. Viruses are generally classifi ed according to the type of their nucleic acid, their protein structure, and whether or not they have a lipid-containing envelope surrounding the viral particle. In general, most viruses gain entry into the lungs via the conducting airways. In nonprimate mammalians these infections are most prominent in the cranioventral lung lobes because of their horizontal position. Table 24 .1 lists some of the major viruses that cause pneumonia and other lung diseases in animals.

Poxviruses are DNA viruses that belong to the Poxviridae family. These viruses are capable of infecting a variety of species including human and some mammalians, including monkeys, rabbits, and squirrels, as well as reptiles and birds. They are regarded as oncogenic since they lead to proliferation of epidermal and occasionally mesenchymal tissues. Poxviridae are highly epitheliotropic and cause cutaneous and/or systemic disease. Infections in the lung of squirrels (Bangari et al. 2009 ) may manifest as tumorlike nodules (Fig. 24.1 ). Histologically, a papillary growth pattern of cuboidal cells that might be type II pneumocytes may be seen ( Fig. 24 .2 ). These cells often contain intracytoplasmic eosinophilic inclusion bodies ( Fig. 24 .3 ).

Herpesviridae is the name of a family of enveloped, double-stranded DNA viruses with relatively large complex genomes. They replicate in the nucleus of a wide range of vertebrate hosts, including horses, cattle, mice, pigs, chickens, turtles, lizards, and fi sh, and even some invertebrates, such as oysters. In many species there are strains of the virus that specifi cally target the respiratory system including dogs, cats, cattle, horses, and chickens. In these species, the virus can target the upper but also the lower respiratory tract, predisposing the host to secondary bacterial infection through impairment of lung defenses.

Equine multinodular pulmonary fi brosis is caused by the equine herpesvirus 5 (EHV-5), a γ-herpes virus. Infected lungs manifest two distinct gross patterns of disease. A pattern of numerous coalescing nodules that are pale white and moderately fi rm ( Fig. 24.4 ) is the most common. In some cases, the growth pattern is that of multiple discrete nodules (Fig. 24.5 ) . Histologically, the lungs show severe interstitial fi brosis, accompanied by a mixed infl ammatory infi ltrate. The majority of the infl ammatory cells are lymphocytes, as well as macrophages, neutrophils, and occasionally eosinophils. The alveolar spaces contain moderate numbers of neutrophils and macrophages. Macrophages with eosinophilic cytoplasm and large eosinophilic intranuclear inclusion bodies (Williams et al. 2007 ) can be seen. Equine herpesvirus 1 (EHV-1) may cause vasculitis leading to abortion, stillbirth, encephalomyelopathy, and respiratory disease. Fatal nonneurological EHV-1 infection in young adult horses does occur but is rare. Gross fi ndings in the lung of a nonneurological EHV-1 infection may include severe edema ( Fig. 24 .6 ) and hydrothorax. Histological examination usually reveals pulmonary edema and perivascular hemorrhage while the alveolar spaces 

Cytomegaloviruses (CMV) are host-specifi c viruses. They are pathogenic to various species including cats, cattle, ground squirrels, guinea pigs, horses, mice, monkeys, sheep, and swine. They affect the lung as well as multiple other organs. Rarely, the lung may be the only affected organ (Hoover and Thacker 1979 ) . CMV infections are most often latent, but under appropriate circumstances, they may result in severe and often fatal infections. In monkeys several patterns of lesions with focal, diffuse, and a mixed pattern of disease have been reported. The lungs with the diffuse pattern of disease seen in monkeys (Baskin 1987 ) and sheep (Hoover and Thacker 1979 ) are heavy, wet, and consolidated. Microscopically, focal lesions show interstitial thickening and prominent hypertrophic pneumocytes. The alveolar spaces contain proteinaceous exudate with macrophages, neutrophils, and multinucleated giant cells with intranuclear basophilic inclusion bodies (Figs. 24.10 and 24.11 ) and occasionally necrotic foci. Microscopic changes in the diffuse forms are similar to those seen in the focal pattern but are generally more severe with chronic organizational changes (Baskin 1987 ) . Electron micrographs illustrate virus present within the cell nucleus ( Fig. 24 .12 ) and viral budding from membranes ( Fig. 24 .13 ). 

Infl uenza is a term used to refer to an infection and/or disease syndrome caused by any type of A infl uenza virus. The infl uenza virus is capable of infecting birds as well as some mammalian species (Easterday et al. 1997 ) . A variety of tissues besides respiratory tissue can be affected and the clinical manifestations are protean (Acland et al. 1984 ; Chaves et al. 2011 ; Woo et al. 2011 ). Compared to other tissues, the severity of the lesions reported in the respiratory system is relatively milder (Chaves et al. 2011 ) . While severe infl ammation occurs in non-respiratory tissues, only hemorrhage can occur in the lung. Hemorrhages in the parabronchi ( Fig. 24 .14 ), atrial spaces, and atrial walls can also be seen ( Fig. 24.15 ). 

Measles virus infects several species of monkeys including rhesus, baboons, and marmosets. In some species, such as marmosets and colobus monkeys, measles infection is more severe resulting in primary giant cell pneumonia followed by secondary bacterial bronchopneumonia (Jones et al. 1997 ) . Histological fi ndings include necrotizing bronchiolitis, diffuse alveolar injury, and prominent perivascular and peribronchial lymphoid tissue (Fig. 24.17 ) . The presence of multinucleated giant cells containing intranuclear and intracytoplasmic eosinophilic inclusion bodies is a characteristic fi nding (Fig. 24.18 

Distemper is an RNA virus that belongs to the Morbillivirus genus group within the family of Paramyxoviridae . Distemper affects multiple species including dogs, wolves, coyotes, ferrets, fox, minks, raccoons, and various aquatic mammals such as dolphins and seals (Kennedy 1998 ) . The virus targets and damages epithelial, mesenchymal, neuroendocrine, and hematopoietic cells in various organs. Secondary bacterial and mycoplasma infections are common in terrestrial mammals. Pneumonia is the predominant pathologic process in infected dolphins. In lungs of aquatic Low-magnifi cation photomicrograph of a rhesus monkey lung infected with measles virus. Note prominent perivascular lymphoid cuffi ng, some collapsed alveoli, and some alveoli fi lled with desquamated pneumocytes mammals, cartilage plates are present adjacent to bronchioles (Fig. 24.19 ) . The pneumonia is a bronchointerstitial pneumonia with presence of serofi brinous exudate and a mixed population of infl ammatory cells in the conducting airways and the alveolar spaces. There is also diffuse alveolar injury with formation of hyaline membranes, hemorrhages, and proliferation of type II pneumocytes (Fig. 24.20 ) . Occasionally syncytial cells are noted in the alveoli and conducting airway cells. Eosinophilic cytoplasmic and nuclear inclusions are observed in type II pneumocytes, in bronchiolar and bronchial cells. Immunohistochemical studies have demonstrated distemper antigens in cells of conducting airways, pneumocytes and mononuclear cells. Interstitial fi brosis is apt to occur in chronic stages of the disease.

A common but serious disease in dogs, distemper is caused by a morbilliform distemper virus. The distemper canine virus enters the lung through the upper airways. Affected lungs are heavy and edematous. Microscopically, necrotizing bronchiolitis, desquamation of respiratory airway cells, and hyperplastic type II pneumocytes can be seen. Histologically, canine distemper is further characterized by interstitial infi ltration by mononuclear cells (Fig. 24.21 ) . Large multinucleated giant cells are often noted (Fig. 24.22 ). Eosinophilic cytoplasmic and nuclear inclusion bodies are seen in type II pneumocytes and alveolar macrophages. 

The Nipah virus, a virus of the Paramyxoviridae family, is carried primarily by fruit bats and affects both humans and swine. In pigs, gross examination of infected lungs shows prominent consolidation of the ventral portion of the lung lobes (Fig. 24.23 ) and also lining of the trachea. The tracheal surface is lined by pseudomembranous membranes (Fig. 24.24 ). There is also evidence of bronchial and bronchiolar infi ltration by lymphocytes, some neutrophils, macrophages, and multinucleated syncytial cells (Fig. 24.25 ) . Intracytoplasmic eosinophilic inclusion bodies are seen in syncytial cells (Hooper et al. 2002 ) . The formation of syncytia within endothelial and epithelial cells can be seen both in cases of Nipah and Hendra virus infections and is related to the fusogenic properties of viral glycoproteins G and F (Weingartl et al. 2009 ). Immunohistochemistry is helpful to demonstrate the presence of the virus in respiratory epithelium (Fig. 24.26 ) , vascular endothelium, and lymphocytes ( Fig. 24.27 ) (Middleton et al. 2002 ) . 

The Hendra virus causes a severe respiratory disease in both horses and humans (Murray et al. 1995 ; Paterson et al. 1998 ) . The virus is carried by species of fruit bats (Young et al. 1996 ) . In horses, gross findings of the lungs include prominent pulmonary edema and dilation of subpleural lymphatic network (Hooper et al. 1997 ) . Histological findings are varied, including mild to moderate interstitial edema, mild infiltration by mononuclear cells (Fig. 24.28 ) , presence of alveolar macrophages, hemorrhagic foci, and capillary thrombosis as well as the presence of syncytial cells and eosinophilic inclusion bodies. Immunohistochemistry studies have demonstrated the presence of Hendra virus antigen in endothelial cells (Fig. 24.29 ).

Feline infectious peritonitis (FIP) is caused by a coronavirus that typically leads to vasculitis. In turn, the vasculitis results in systemic infl ammatory disease. The virus may also cause chronic immunologic mediated disease. It has two forms, effusive and noneffusive forms. In cats, about 25 % of the infected population harbor a pleural effusion. The effusions generally contain a large amount of yellow, viscous fl uid and fi brin strands. There are gray-white granular membranous deposits of exudate on the pleural surface and severe pulmonary edema. Microscopic fi ndings include generalized vasculitis, hemorrhagic perivasculitis, and edema ( Fig. 24 .30 ) plus multiple pyogranulomas made up of neutrophils, lymphocytes, and macrophages (Fig. 24.31 ) (Dungworth 2007 ) . 

A unique lung disorder affecting the lungs of sheep is ovine pulmonary adenocarcinoma (OPA). The disorder has a wide geographic distribution and is also known as jaagsiekte, a word derived from the Afrikaans word meaning "driving sickness." The causal agent is the RNA jaagsiekte sheep retrovirus (JSRV), currently regarded as a betaretrovirus (Griffi ths 2010 ). The age of affected sheep varies widely from 2 months to 11 years. Initially OPA was regarded as a proliferative disorder with metastatic potential (Nobel (Perk et al. 1974 ) . Clinically, the disease progresses slowly. Initial manifestations include coughing and exercise intolerance, followed by wheezing, nasal discharge, and crackles. Grossly, white fi rm consolidated pulmonary nodules are present (Fig. 24.32 ). Histological examination generally shows papillary and acinar structures lined by columnar to cuboidal cells replacing the alveolar spaces of the lung (Fig. 24.33 ). Immunohistochemical studies show the presence of surfactant proteins in the majority of affected cells that generally correspond to type II alveolar cells (Platt 2002) . Some cells are known to express CC10, a protein of Clara cell origin. Ultrastructural studies have demonstrated the presence of lamellated membrane structures within type II pneumocytes (Fig. 24.34 ).

Ovine progressive pneumonia is caused by the maedi-visna virus, a member of the lentivirus genus within the Retroviridae family. Sheep and occasionally goats can be affected with a chronic progressive pneumonia. Grossly, the lungs do not collapse and show fi rm large white consolidated foci (Fig. 24.35 ) . Histologically, the pneumonia is characterized by the presence of perivascular, peribronchial, and peribronchiolar areas of lymphofollicular proliferation ( Fig. 24.36 ). Interstitial infi ltration by lymphocytes, interstitial fi brosis, and smooth muscle hyperplasia can also be seen (Fig. 24.37 ). There is in addition hyperplasia of pulmonary lymph nodes with formation of germinal centers within the lymphoid follicles (Lairmore et al. 1986 ). Electron microscopic examination shows the presence of viruses with features of lentiviruses. 

Simian immunodefi ciency virus (SIV) is a lentivirus in the family of Retroviridae. Infections secondary to SIV occur spontaneously and asymptomatically in several species of monkeys and macaques, the latter sometimes developing an immunodefi ciency syndrome (Baskin et al. 1991 ). Gross fi ndings in the lungs include diffuse pleural thickening, with some irregular fi rm foci of consolidation. The lesions seen in early stage of the infection tend to be localized. Microscopically, perivascular infi ltration by lymphocytes and histiocytes around small vessels (Fig. 24 .38 ) as well as infi ltration of the alveolar septa by mononuclear infl ammatory cells (Fig. 24 .39 ) can be seen. Syncytial multinucleated giant cells occur during the stage of rapid multiplication (Fig. 24.40 ).

In advanced infections the lesions are diffuse and/ or patchy (Fig. 24 .41 ) and are associated with alveolar spaces fi lled with exudate that include fi brin, histiocytes, lymphocytes, plasma cells, neutrophils, and syncytial cells (Fig. 24.42 ).

In advanced stages there is mild fi brosis of the alveolar septae and fi brosis of the visceral pleura (Baskin et al. 1991 ) . Mature virions are present in cytoplasmic vacuoles in syncytial cells and macrophages ( Fig. 24.43 ) . 

Lesions in broiler and layer chickens in an outbreak of highly pathogenic avian infl uenza virus infection

Cutaneous and systemic poxviral disease in red ( Tamiasciurus hudsonicus ) and gray ( Sciurus carolinensis ) squirrels

Cytomegalovirus infection in immunodefi cient Rhesus monkey

Lentivirus-induced pulmonary lesions in rhesus monkeys ( Macaca mulatta ) infected with simian immunodefi ciency virus

Pathogenesis of highly pathogenic avian infl uenza A virus (H7N1) infection in chickens inoculated with three different doses

Fetal nonneurological EHV-1 infection in a yearling fi lly

Feline infectious peritonitis

Infl uenza. In: Calnek BW (ed) Diseases of poultry

Pathology and pathogenesis of ovine pulmonary carcinoma

Lesions of experimental equine morbillivirus pneumonia in horses

Comparative pathology of diseases caused by Hendra and Nipah viruses

Ovine pulmonary cytomegalovirus

Measles (rubeola, monkey intranuclear agent, morbillus)

Morbillivirus infections in aquatic mammals

Ovine lentivirus lymphoid interstitial pneumonia. Rapid induction in neonatal lambs

Experimental Nipah virus infection in pigs and cats

A morbillivirus that cause fetal disease in horses and humans

Histological pattern of the metastasis in pulmonary adenomatosis (jaagsiekte)

Zoonotic disease in Australia caused by Novel member of the paramyxoviridae

Pathology of laboratory rodents and rabbits

Biochemical and morphological evidence for the presence of an RNA tumor virus in pulmonary carcinoma of sheep (jaagsiekte)

Alveolar type II cells expressing jaagsiekte sheep retrovirus capsid protein and surfactant are the predominant neoplastic cell type in ovine pulmonary adenocarcinoma

Animal models of henipavirus infection: a review

Equine multinodular pulmonary fi brosis: a newly recognized herpesvirus-associated fi brotic lung disease

Comparative histopathological characteristics of highly pathogenic avian infl uenza (HPAI) in chickens and domestic ducks in

Serological evidence for the presence in Pteropus bats of a paramyxovirus related to equine morbillivirus