Inclusion body disease of giant snakes

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Idol snake ( Boa constrictor )

The inclusion body of the boas ( "boid inclusion body disease" BIBD , also called inclusion body (EK) of the Boas or Boide EK) is a fatal infectious disease , which in Boas (boidae) and pythons occurs (Pythonidae). Due to the increasing number of cases, BIBD is now the most important infectious disease in snakes in captivity. It was first seen in animals in private collections and zoological gardens in the United States in the late 1970s, and later in Africa and Europe . Retroviruses had come into focus as pathogens since 1994 , as virus-like particles of the retroviral C-type were found in the cells of almost all infected organs of the animals in addition to the typical inclusion bodies . Further studies have shown that this is not tenable. Since 2012, a viral infection with various newly discovered viruses of the genus Reptarenavirus (family Arenaviridae ) has been assumed to be the cause of the disease. These newly created viruses are very likely as so-called emerging viruses, genetic new combinations and variants of arenaviruses that were not previously disease-causing in snakes.

The viral infection in adult snakes is insidious, chronic and in the first weeks and months with little or no clinical symptoms. During this time, it is very likely that it can be transmitted to other animals through smear infection from animal to animal or through contact with infected objects. In boas, transmission from the mother to the young is also possible. Transmission by snake mites ( Ophionyssus natricis ) as a vector is also discussed. The diseased snakes die of severe neurological disorders that prevent them from eating. Since neither specific antiviral therapy nor preventive vaccination are available, the only available measures to contain the infection are a strict three to six month quarantine , compliance with hygiene in keeping ( disinfection of objects and hands) and the killing of sick animals. Strict isolation of infected but not yet sick animals is possible.

etiology

Histopathology

  • Liver specimen of a boa constrictor with BIBD ( HE , 1000x magnification). Eosinophil EC in liver cells (selected EC marked with arrows). Additional bacterial infiltration with acute liver cell necrosis (dark areas, lower left).

  • Immunohistochemical preparation of the pancreas of a boa with BIBD: EK dark red with monoclonal anti-IBD protein antibodies stained (arrows), counter-stained cell nuclei blue, beam 20 microns (L.-W. Chang et al, 2013.).

TEM image of an inclusion body in the kidney cell of a boa constrictor (bar 1 µm). The preparation was in addition to the negative staining ( uranyl acetate ) with labeled gold , anti-IBD antibodies stained protein, the binding can be identified by the small black dots inside the large EK (L.-W. Chang et al. 2013) .

In the first case descriptions of the BIBD, the so-called inclusion bodies (EK) stood out as a special histological feature . They were found in very different cell types of almost all organs, in boas in very high numbers in epithelial cells of all organs of the gastrointestinal tract (including pancreas , liver , tonsils of the esophagus ), in the epithelium of the respiratory tract , in tubular cells of the kidneys and in nerve cells of the central nervous system (im Difference to pythons in boas also in glial cells ). An increased number of detectable lymphocytes in the surrounding tissue can only be observed in a few cases as a sign of an inflammatory reaction .

The EK as a histopathological change are characteristic of a number of different infections with intracellular pathogens such as viruses, so that according to these initial findings, a ( systemic ) virus infection affecting the entire organism was suspected as the cause of the disease. The ECs occurring in the cytoplasm in BIBD can be stained with the acidic dye eosin ( eosinophil ) in the hematoxylin-eosin staining , which indicates a basophilic property of the EC. In electron microscope images, the very dark (electron dense) appearing ECs originate from polyribosomes and the edge of large ECs is often surrounded by a ring of smaller, constricting ECs. Occasionally, concentric structures can be observed within the EC. An approximately 68 kDa protein could be identified as the main component of the inclusion bodies . Specific antibodies against this so-called IBD protein have been detected in the blood of diseased snakes. With monoclonal antibodies against this protein, the inclusion bodies can be specifically stained and displayed in immunohistological staining of tissue samples (see figure).

Pathogen

In 1994, in electron micrographs, Schumacher discovered membrane-coated, virus-like particles within the histologically altered cells. The particles were 110 nm in diameter and had a hexagonal, possibly icosahedral capsid inside . These virus particles could not be observed outside the cell. Similar particles were found in primary kidney cell cultures of diseased idol snakes. After injecting cell-free supernatants from these cell cultures into two dark tiger pythons ( Python molurus bivittatus ), the animals developed BIBD and exhibited the typical EK in the tissue. However, the particles previously observed could no longer be found. Due to their size and the concentric capsid, Schumacher assumed that they could be retroviruses with a so-called C-type morphology ( alpharetroviruses ). Wozniak and colleagues then infected healthy boas with homogenized liver tissue from a diseased idol snake, which they had previously filtered (pore size up to 45 µm). The snakes showed the typical EC after about ten weeks, the virus-like particles could be observed again, but the animals showed no signs of disease even after one year. Two of Koch's three postulates proving a pathogen as the cause of the disease were thus not fulfilled. A later study on the occurrence of retroviruses in BIBD-affected snakes could not show a connection between virus presence and disease. Retroviruses, especially endogenous retroviruses , are often found in amphibians and reptiles , and genome sequences of endogenous retroviruses of the C-type are also widespread in reptiles. Although retroviruses are able to trigger tumor diseases in snakes, these viruses can also be observed in cells of healthy pythons without any disease-causing significance. Another argument against a retrovirus as the pathogen of BIBD is that the formation of large cytoplasmic inclusion bodies is atypical for these viruses.

Schematic structure of an arenavirus: The genome is in two separate segments, the L (arge) and S (mall) segments, which are each encased by the helically arranged nucleoprotein.

The search for a pathogen took a new turn in 2012 when two viruses and another incomplete viral genome sequence were identified in diseased idol snakes and ringed boas , which appeared to belong to the family Arenaviridae due to their sequence similarity and their genome structure . This was achieved with a more modern method, metagenome analysis and sequencing with a deep sequencing technique. This was the first detection of viruses Arena outside of mammals as host . The newly discovered virus isolates were named Golden Gate Virus (GGV) and California Academy of Sciences Virus (CASV). Within the Arenaviridae , the two viruses are clearly different from the previous genera, among other things, the viral glycoproteins of the virus envelope are more similar to those of the Filoviridae than the previously known Arenaviruses. A further working group independently confirmed the results shortly afterwards in diseased idol snakes, in primary cell cultures and through structural analyzes of the virions . They found another arenavirus very similar to GGV and CASV, the University of Helsinki virus (UHV). Another study in the same year identified the Boa arenavirus NL B3 (now called ROUT virus ), which, based on sequence comparisons, is closest to UHV. As a new virus genus to be created, the discoverers of the UHV suggested the virus group of the Boid Inclusion Body Disease-associated Arenaviruses (BIBDAV), but the International Committee on Taxonomy of Viruses added the new genus to the taxonomy as Reptarenavirus .

After purification of the 68 kDa protein (IBD protein) from infected, primary snake cell cultures and a subsequent protein analysis using mass spectrometry ( MALDI-TOF ), it was identified as a viral nucleoprotein of reptarena viruses. Its size is in the range of the nucleoproteins of other arenaviruses (63 to 68 kDa), which are also located on membranes in the cytosol and are associated with the replication of the viral RNA. In addition to this function as an important component of the replication complex ( viroplasma ), the nucleoprotein also makes up the bulk of the virions with around 70%. Like all viral nucleo- and capsid proteins, it is basic, which explains the long-known eosinophilic, basophilic property of inclusion bodies.

Many more new arenaviruses were identified in Abgottschlangen in 2015 and associated with the BIBD. These included the University of Giessen virus (UGV), Tavallinen-Suomalainen-Mies virus (TSMV), Hans-Kompis virus (HKV) and Suri-Vanera virus (SVaV), all of which are the new viruses in the genus Reptarenavirus are very similar. However, one virus, the Haarman Institute Snake Virus (HISV), did not fit into this genus due to the sequence analysis and therefore the ICTV established another new genus Hartmanivirus ( sic !) In the Arenaviridae family for this species . Of these viruses, however, only the large of the two genome segments, the L segment, was used for sequence analysis. It has not been conclusively clarified whether these individual viruses can all be addressed as separate species or only subspecies or subtypes.

Compared to other viral infections, the finding is unusual that in animals with BIBD always a mixture of different reptarena viruses or several different variants of a virus species are isolated at the same time. A study of the variance, distribution and transmission of these viruses demonstrated various mechanisms that can explain the observed variability. This includes a reassortment of the two arenaviral RNA segments, an intrasegmental recombination between the same segments of different virus isolates and a high mutation and replication rate in the newly infected animal. After natural contact transfer from a diseased to a non-infected snake, a uniform virus strain was initially detectable in the newly infected animal, which split into several, clearly different virus strains within a few weeks until the disease broke out. In all animals examined, a total of 23 different genotypes of the L-segment and 11 of the S-segment were identified, with only one S-segment genotype always predominating in an individual animal as well as in a certain population of snakes. In the overwhelming number of cases (77% of infections), the S genotype 6 was detected, which could have a particularly high replication rate or an optimized cell entry. The extent of the diversity of the virus strains present here and the speed of their recombination is not known from other virus infections in animals and humans.

Origin of the viral pathogen

The keeping of giant snakes in zoological gardens and traveling menageries has been known in Europe and America since the 19th century, and keeping them in terrariums by private individuals has been increasingly common since the 1950s. Despite the long history of keeping snakes, no illness was reported prior to the late 1970s that was similar to the fatal and characteristic course of BIBD. In addition to the recurrence of a previously unknown disease, virological properties also suggest that the infection was caused by the pathogen jumping over from a still unknown natural host to giant snakes kept in captivity. Typical of the disease progression of a virus emerging in an animal population is its often not yet optimized transmission capacity (low contagiousness ), a severe disease progression or a high lethality as well as a high variability of the pathogens in the new host. The adaptation to a new host is particularly favored by an increased population density of the hosts, which decisively increases the probability of multiple transmissions of the pathogen between the new hosts even in the absence of the original source of infection. This circulation within the new host population can lead to an improvement in the ability to transmit and replicate ( “replicative fitness” ) of new viruses and thus establish the infection permanently in the new host species. This circulation, also known as “viral traffic” , is crucial in the establishment of new, so-called emerging viruses (“newly emerging viruses”). By intensifying animal-to-animal contact in captivity with larger groups of animals, new pathogens can be given a more favorable opportunity to circulate than under natural conditions, since giant snakes living in the wild are loners .

The most important examples of such a host transition in humans are the human immunodeficiency viruses , the henipaviruses , the influenza A virus H5N1 or the MERS coronavirus , in domestic animals the canine parvovirus 2 . Arena viruses such as the Lassa virus or the lymphocytic choriomeningitis virus (LCMV) are known for cross-species infections due to their genetic variability and their low host and cell specificity ( tropism ). In the case of the Lassa virus, transmission from rodents to humans is possible if the rodents are used for food, so that a transfer of the new arenaviruses through fed rodents to the giant snakes appeared possible.

The arenaviruses isolated by the BIBD can not only multiply in cell cultures with snake cell lines , but also in mammalian cells, due to the low level of tropism . In this reproduction of the University of Helsinki virus (UHV) in Vero cells (from green monkeys ) and in human A549 cells , the virus adapted to the new cells after only three passages and increased its replication rate. It was surprising that the reproduction of UHV in snake and mammalian cells is completely inhibited at 37 ° C, while optimal reproduction conditions prevail at 30 ° C. From this it can be concluded that the ability of these viruses to reproduce is adapted to the body temperature of cold-blooded animals such as reptiles and amphibians. This, as well as the considerable differences between the reptarena viruses and the known arenaviruses in mammals (especially rodents) in the so-called Z protein and the envelope proteins , would make an origin of the BIBD-associated viruses from other mammals appear unlikely. Theoretically, a possible source is an entry about giant snakes living in the wild or other snake species in which original reptarena viruses have been adapted and do not cause an infectious disease, i.e. in which the infection is not clinically recognized. Likewise, other reptiles or amphibians, which come into non-natural contact with giant snakes in human animal husbandry, are conceivable as the original host. The evidence of frequent reassortments and recombinations of the virus genome allows the assumption that the pathogenic reptarena viruses were most likely caused by new combinations of originally non-pathogenic viruses in free-living giant snakes. This would be facilitated by an unnaturally dense animal contact in the keeping and the constant introduction of wild animals with naturally occurring color variants of the scale skin (so-called "color morphs" ) that are very popular with breeders . The reptarenaviruses possibly occurring in nature could be subject to the same geographically different coevolution between reservoir host and snake virus , as is known from other arenaviruses, and thus increase the variability of new reptarenaviruses through recombination. After the animals have been brought together in captivity, the geographically different variants can eventually give rise to new, pathogenic reptarena viruses.

transmission

Snake mite Ophionyssus natricis , a possible vector of inclusion body disease (drawing)

The main transmission route has not yet been sufficiently clarified. Direct smear infection from animal to animal and indirect transmission through contaminated objects and hands when handling the snakes are very likely . Transmission from mother to young is suspected in boas, although it is unclear whether close contact is sufficient for this or whether a real vertical infection plays a role. Excretions such as saliva and vomit from sick animals are considered to be potentially infectious. Since the spread within an animal community is comparatively slow, transmission via the air is considered unlikely. The slow transmission also indicates that the pathogen is not very contagious . What is striking is the increased occurrence of BIBD in positions that are infested with the blood-sucking snake mite Ophionyssus natricis . This led to the assumption that these ectoparasites could at least be involved in the transmission. Proof of this assumption, for example by detecting the viruses in the parasite or by experimental transmission, has not yet been provided (as of 2016). Since both the BIBD and the snake mite infestation are favored by unclean animal husbandry, this could also explain the observed coincidence.

The disease can be transmitted experimentally to snakes when ultrafiltered cell culture supernatant from primary cell cultures from tissue of diseased snakes is injected into a test animal. A transfer with centrifuged, cell-free organ suspensions of a diseased idol snake ( Boa constrictor ) to tiger pythons is experimentally possible. There is no evidence of the Reptarenavirus being transmitted to humans.

Occurrence

The BIBD occurs only in boas and pythons, whereby the frequency in boas is much higher. Comprehensive studies on the prevalence are not yet available; only the study of animal groups of different sizes, mostly kept together in one facility, has been published. A post-mortem study in the USA showed a prevalence of more than 33% in various subspecies of the idol snake and 28% in the ringed boa ( Corallus annulatus ), while BIBD was not detected in the 301 pythons examined. The prevalence in bottom-dwelling giant snakes ( Acrantophis spp., Epicrates spp. And Eunectes spp.) Was very low . An examination by the Veterinary Investigation Office of Ostwestfalen-Lippe found BIBD-typical histological changes in the section of 575 Boidae in only 2% of the pythons examined, but in 47% of the boas. In an examination of 100 living and initially clinically inconspicuous snakes from 14 different postures in Germany, BIBD was found in 3 of 32 idol snakes, 2 of 16 tiger pythons and 1 of 4 reticulated pythons .

After the infection was described as an independent disease, it was initially found most frequently in the dark tiger python ( Python molurus bivittatus ). The BIBD was then detected in 1998 in caught diamond pythons ( Darwin carpet python Morelia spilota variegata and diamond python Morelia spilota spilota ) in Australia, in idol snakes ( Boa constrictor ) in the Canary Islands and in Belgium. Further cases of BIBD were described in various other species in the 2000s: Great anaconda ( Eunectes murinus ), yellow anaconda ( Eunectes notaeus ), rainbow boa ( Epicrates cenchria ), Haiti boa ( Epicrates striatus ), northern Madagascar boa ( Acrantophis madagascariensis ), Heller Tigerpython ( Python molurus molurus ), reticulated ( Python reticulatus ) and python ( Python regius ). Due to the worldwide exchange and trade with giant snakes, which leads to an undetected spread of the infection, BIBD is now possible worldwide for every corresponding keeping of the animals. So far, BIBD has only been observed in giant snakes that have been kept in captivity. It is unclear whether this disease also occurs in wild snakes.

Very similar histological changes with the same lethal course were observed in a group of March's palm-lance vipers ( Bothriechis marchi ) and one chain snake ( Lampropeltis getula ), although the unambiguous assignment to the identical or a BIBD-like infectious disease is still pending. The electron microscopic examination of these animals showed a different morphology of the cell and inclusion bodies than the BIBD.

Course of disease

Clinical symptoms

The infection is initially asymptomatic, the onset of the disease after an incubation period of weeks or usually months begins with unspecific signs such as passivity, withdrawal behavior or low food consumption ( inappetence ) of the animals. In boas, recurrent regurgitation of stomach contents several days after ingestion is often the first more specific sign of BIBP. This is often followed by complete refusal to eat ( anorexia ) and sometimes irregular, frequent moulting . After a few weeks, conspicuous neurological symptoms appear as signs of an infection of the central nervous system (CNS), which, together with the regurgitations, are regarded as typical of BIBD. These include restricted spatial orientation (disorientation), head tremor , ataxia , flaccid paralysis , atypically twisted postures with a rigid, bent head posture and an opisthotonus with muscle spasms. Partially supine posture and the inability to move from a supine position back to the natural prone position are very characteristic. The latter is also used as a clinical sign during a veterinary examination. The neurological disorders make it impossible for the snake to strangle its prey. In boas, death occurs several weeks after the first clinical signs of disease appear, but sometimes only months later.

Pythons do not show regurgitations, but often anorexia. In contrast to boas, the neurological symptoms appear earlier and more severe. Typical of pythons are the star-gazing phenomenon , in which the head is rigidly directed upwards, the tipping over of the head, individual seizures and paralysis of the rear half of the body. The clinical course in pythons is faster overall, so that death occurs a few weeks after the onset of the disease.

In addition to the neurological symptoms in all giant snakes, there are other symptoms as a sign of virus-induced immunodeficiency , which are usually caused by co-infection with additional (possibly opportunistic ) bacterial and viral pathogens. These include pneumonia , ulcerative stomatitis ( snakes' mouth rot ), necrotizing, multifocal dermatitis , bacterial granulomas in the liver and kidneys, and osteophytes of the vertebral bodies . Virus-induced immunodeficiency, along with the earlier assumption of retroviral infection, led to the misleading popular science term Boa AIDS or Snake AIDS for BIBD. Tissue growth and tumor diseases are also observed during BIBP. Thus, sarcomas of the skin and leukemia was observed in the BIBD. After the identification of the BIBD-associated arenaviruses, a virus was isolated from the tumor tissue of a fibromyxoma of a BIBD-afflicted idol snake, which probably represents a subtype of the California Academy of Sciences virus.

Laboratory findings

In the case of acutely infected animals in the initial phase of the disease, the examination of clinical-chemical and hematological parameters may show abnormalities which, however, are not specific to the disease and are therefore not diagnostic. These include an increase in the number of leukocytes in the blood ( leukocytosis ) and a percentage increase in the proportion of lymphocytes (relative lymphocytosis ) as general inflammation parameters . Signs of liver involvement are decreased values ​​for total protein and globulins in the serum, as well as increased aspartate aminotransferase concentrations in the serum. The latter, in particular, is not observed to this extent in chronic courses.

Diagnosis

Histological diagnosis

Blood smear from a boa constrictor with BIBD. 1 to 2 µm in diameter, basophilic (blue) inclusion bodies in erythrocytes (arrows), Wright-Giemsa stain, 1000 times magnification

The diagnosis of BIBD can be made by histological examination of tissue samples, tissue swabs from the oral mucosa, and heparin whole blood . Liver biopsies or tissue samples from glandular tissue ( pancreas ) can be used in living animals , but their extraction under general anesthesia is not low-risk and is very complex. The esophageal tonsils are well defined in giant snakes and more easily accessible endoscopically for a biopsy. For assessment, the fixed and sectioned tissue samples are stained with the HE or Wright-Giemsa stain . Microscopic evidence of the typical eosinophilic inclusion bodies in the liver, glandular tissue, and blood lymphocytes indicates BIBP. Inclusion bodies can only be detected in erythrocytes in boas, but not in pythons, and this often even before the onset of the disease. In snakes, heparinized blood is taken from the oral veins or by cardiac puncture .

However, the absence of these signs in a tissue or blood test does not in principle rule out an infection. The disease can be proven beyond doubt by dissecting dead animals, with the typical histological signs, in addition to other organs, mainly being found in brain, liver and pancreas tissue.

Virological diagnostics

A direct pathogen detection of reptarena viruses in tissue smears and tissue samples by means of PCR can be attempted, the informative value of such a detection in practice has not yet been sufficiently tested (as of 2016). The negative predictive value of a PCR for arenaviral RNA, especially in living animals, is still unclear.

Virus cultivation and identification in cell culture can be carried out for research purposes . A serological test for the detection of specific antibodies is not yet available for routine diagnostics. Antibodies against the p68-IBD protein, which is predominantly found in the inclusion bodies, achieved a specificity of 100% and a sensitivity of 83% in serological tests in a study with 93 animals. Reptarenavirus-specific anti- IgM and anti- IgY (the counterpart to IgG in reptiles ) could be isolated experimentally and produced for the production of antibodies for serological detection in immunoblot or direct immunofluorescence testing .

Differential diagnoses

The clinical picture of regurgitation (in Boas) combined with neurological symptoms indicates BIBD, but other diseases with similar symptoms can also occur and can therefore be considered in the differential diagnosis. Regurgitation can be observed in various other infectious diseases of snakes, such as an infection of the digestive tract with amoebas , trichomonads , coccidia , cryptosporidia , various worm infections with roundworms or bacterial gastritis , enteritis and stomatitis . Vomiting of digested food is a common symptom of poisoning . In the event of poisoning with phosphoric acid esters , which are used, among other things, to combat snake mites, vomiting is associated with neurological symptoms. Vomiting is a common symptom in the event of sepsis , a tumor disease, too high an ambient temperature or as a result of violence caused by incorrect handling of the animals. The neurological symptoms also occur in encephalitis of a viral, bacterial or parasitic origin. The most important differential diagnoses are infection with paramyxoviruses (snake paramyxoviruses ATCC-VR-1408 and -1409), which can show neurological and respiratory symptoms, and seizures combined with gastrointestinal symptoms in the case of an invasive infection with Entamoeba invadens or Acanthamoeba species.

Therapy and prophylaxis

Specific antiviral therapy against reptarena viruses is not available, and symptomatic treatment of the neurological disorders is also not possible. Active feeding of the animals that are no longer able to eat independently and the supply of fluids can in some cases improve the general condition, the progression of the infection is not influenced by this. In the case of sick animals with a clear histological diagnosis, killing is recommended, which in snakes can be carried out with intracardiac or intrazolomatic administration of pentobarbital or T61 . The killing prevents slow starvation due to the neurological paralysis that occurs in BIBD. Infected, but not yet diseased boas can be kept in strict isolation. Since vaccination is also not available as a preventive measure against disposition , the measures are limited to the containment of the spread of the infection in the sense of exposure prophylaxis . This is hygienic animal husbandry with disinfection of the contact surfaces, the devices (tongs) and the hands after contact with the animal and generally clean husbandry conditions. Since the reptarenaviruses have a virus envelope , disinfectants with limited virucidal properties are sufficient . These measures also reduce the risk of an infestation with snake mites, which cannot yet be ruled out as possible carriers of BIBD.

Before introducing a new animal into a common husbandry - regardless of a diagnosed disease or an origin from an allegedly BIBD-free breeding - a strict quarantine of at least three to six months is to be observed, whereby six months is always recommended for boas due to the slower development of the disease become. A quarantine of six months offers what is considered to be a sufficient safety period given the very variable incubation period.

literature

  • J. Schumacher et al .: Inclusion Body Disease in Boid Snakes . Journal of Zoo and Wildlife Medicine (1994) 25, 4: pp. 511-524
  • Petra Kölle (Ed.): Pet and patient: Lizards and snakes. Stuttgart (Enke) 2015, p. 215 f., ISBN 978-3-83-041224-3
  • D. Vancraeynest et al .: Inclusion body disease in snakes: a review and description of three cases in boa constrictors in Belgium. Vet. Rec. (2006) 158 (22): pp. 757-760 PMID 16751310
  • LW. Chang and ER Jacobson: Inclusion Body Disease, A Worldwide Infectious Disease of Boid Snakes: A Review. Journal of Exotic Pet Medicine (2010) 19 (3): pp. 216–225 ( PDF )

Web links

Commons : Boid Inclusion Body Disease  - Collection of Pictures, Videos and Audio Files
  • Images on Researchgate (from: LW. Chang and ER Jacobson, 2010)
  • The Joint Pathology Center (Silver Spring, Maryland, USA) Case descriptions with complete histological specimens:

Individual evidence

  1. ↑ J. Schumacher et al. (1994)
  2. ↑ MK Axthelm: Clinicopathologic and virologic observations of a probable viral disease affecting boid snakes . Proc. Annu. Meet. At the. Assoc. Zoo Vet. (1985): pp. 108-109 (abstract)
  3. ↑ J. Schumacher et al. 1994, p. 511
  4. ↑ L.-W. Chang and ER Jacobson, 2010, p. 218
  5. ^ ER Jacobson and DA Samuelson: Identifying reptil pathogens using electron microscopy . In: ER Jacobson (Ed.): Infectious Diseases and Pathology of Reptiles: A Color Altlas and Text , CRC Press, Boca Raton, 2007, ISBN 978-0-84-932321-8 , pp. 299 ff
  6. ↑ a b E. Wozniak et al .: Isolation and characterization of an antigenically distinct 68-kd protein from nonviral intracytoplasmic inclusions in Boa constrictors chronically infected with the inclusion body disease virus (IBDV: Retroviridae) . Veterinary Pathology (2000) 37 (5): pp. 449-459 PMID 11055868
  7. ↑ L.-W. Chang et al .: Immunohistochemical detection of a unique protein within cells of snakes having inclusion body disease, a world-wide disease seen in members of the families Boidae and Pythonidae. PLoS One (2013) 8 (12) PMID 24340066
  8. ↑ J. Schumacher et al. : Inclusion Body Disease in Boid Snakes . Journal of Zoo and Wildlife Medicine (1994) 25, 4: pp. 511-524
  9. ↑ JB Huder et al. : Identification and characterization of two closely related unclassifiable endogenous retroviruses in pythons (Python molurus and Python curtus) . J. Virol. (2002) 76 (15): pp. 7607-7615 PMID 12097574
  10. ↑ E. Herniou et al. : Retroviral diversity and distribution in vertebrates . J. Virol. (1998) 72 (7): pp. 5955-5966 PMID 9621058
  11. ↑ MD Stenglein et al. : Identification, characterization, and in vitro culture of highly divergent arenaviruses from boa constrictors and annulated tree boas: candidate etiological agents for snake inclusion body disease. MBio. (2012) 3 (4): e00180-12 PMID 22893382
  12. ↑ a b U. Hetzel et al. : Isolation, identification, and characterization of novel arenaviruses, the etiological agents of boid inclusion body disease. J. Virol. (2013) 87 (20): pp. 10918-10935 PMID 23926354
  13. ↑ R. Bodewes et al. : Detection of novel divergent arenaviruses in boid snakes with inclusion body disease in The Netherlands. J. Gen. Virol. (2013) 94 (6): pp. 1206-1210 PMID 23468423
  14. ↑ SR Radoshitzky et al. : Past, present, and future of arenavirus taxonomy . Arch. Virol. (2015) 160 (7): pp. 1851-1874 PMID 25935216
  15. ↑ NL Baird et al. : Arenavirus infection induces discrete cytosolic structures for RNA replication . J. Virol. (2012) 86 (20): pp. 11301-11310 PMID 22875974
  16. ↑ J. Hepojoki et al .: Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease . J. Virol. (2015) 89 (16): pp. 8657-8660 PMID 26041290
  17. ↑ U. Hetzel et al. : Reply to "Updated phylogenetic analysis of arenaviruses detected in boid snakes" . J. Virol. (2014) 88 (2): p. 1401 PMID 24379419
  18. ↑ MD Stenglein et al. : Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections . PLoS Pathog. (2015) 11 (5): e1004900 PMID 25993603
  19. ↑ Elliott R. Jacobson: Snake Inclusion Body Disease . (reptilesmagazine.com)
  20. ^ LP Villareal: Evolution of Viruses . In: Brian WJ Mahy and Marc H. van Regenmortel (Eds.): Encyclopedia of Virology , 3rd Edition, San Diego 2008, Volume 2, ISBN 978-0-12-373935-3 , pp. 174-184
  21. ↑ Stephen S. Morse: Examining the Origins of Emerging Viruses (Section: Emergence as a two-step Process, And the Importance of Viral Traffic ). In: Stephen S. Morse (Ed.): Emerging Viruses . Oxford University Press 1993, ISBN 0-19-507444-0 , pp. 16-20
  22. ↑ J. Ter Meulen et al .: Hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of Lassa virus in the Republic of Guinea . American J. Trop. Med. Hyg. (1996) 55 (6): pp. 661-666 PMID 9025695
  23. ↑ J. Hepojoki et al .: Replication of boid inclusion body disease-associated arenaviruses is temperature sensitive in both boid and mammalian cells. J. Virol. (2015) 89 (2): pp. 1119-1128, PMID 25378485
  24. ↑ MD Stenglein et al .: Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections . PLoS Pathog. (2015) 11 (5): e1004900 PMID 25993603
  25. ↑ J. Schumacher et al., 1994
  26. ↑ D. Vancraeynest et al., 2006, p. 757
  27. ↑ Petra Kölle (ed.): Pet and patient: Lizards and snakes. Stuttgart (Enke) 2015 p. 215
  28. ^ MM Garner, JT Raymond: Methods for diagnosing inclusion body disease in snakes . Proc. of the Association of Reptile and Amphibian Veterinarians Congress, Naples USA, May 8-11, 2004, pp. 21-25. Quoted from: D. Vancraeynest et al .: Inclusion body disease in snakes: a review and description of three cases in boa constrictors in Belgium. Vet. Rec. (2006) 158 (22): p. 758 PMID 16751310
  29. ↑ Petra Kölle (ed.): Pet and patient: Lizards and snakes. Stuttgart (Enke) 2015 p. 215
  30. ↑ M. Pees et al .: Prevalence of viral infections in captive collections of boid snakes in Germany . Veterinary Recorded (2010) 166 (14): pp. 422-425 PMID 20364009
  31. ↑ MS Carlisle-Nowak et al .: Inclusion body disease in two captive Australian pythons (Morelia spilota variegata and Morelia spilota spilota) . Aust. Vet. J. (1998) 76 (2): pp. 98-100 PMID 9578777
  32. ↑ J. Orós et al .: Inclusion body disease in two captive boas in the Canary islands . Vet. Rec. (1998) 143 (10): pp. 283-285 PMID 9787424
  33. ↑ D. et al .: Vancraeynest inclusion body disease in snakes: a review and description of three cases in boa constrictors in Belgium. Vet. Rec. (2006) 158 (22): pp. 757-760 PMID 16751310
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  50. ↑ RS Funk: Differential Diagnoses by Symptoms. Snakes. In: DR Mader (Ed.): Reptile Medicine and Surgery , Philadelphia (WR Saunders) 2nd edition 2005, ISBN 978-0-72-169327-9 , pp. 405 and 675 f
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  54. ↑ EAZWV Transmissible Disease Fact Sheet No. 34 , recommendation of the European Association of Zoo and Wildlife Veterinarians , as of 2009 (pdf)
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