Detection of Virus-Like Particles in the Liver of Black and White Ruffed Lemurs With Hepatitis

Worley, Michael B.; Stalis, Ilse H.

doi:10.7589/0090-3558-38.2.258

Cited by 4 publications

(4 citation statements)

References 16 publications

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“…Hepatocellular iron storage may become severe enough to lead to alterations in hepatocellular function (hemochromatosis) compromising pharmocologic studies. In lemurs, hepatocellular iron is thought to play a role in the development of spontaneous hepatocellular carcinomas, but recently a virus has also been identified (9,118). Nodular foci of extramedullary hematopoiesis and myelolipomas are occasionally found in NW monkeys.…”

Section: Gastrointestinal Tractmentioning

confidence: 96%

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A Primer of Primate Pathology: Lesions and Nonlesions

Lowenstine

2003

Toxicol Pathol

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Nonhuman primates are important laboratory animals for biomedical, pharmacology, and toxicology research. To effectively use primates as models, their gross and histologic anatomy, physiology and natural history, as well as common health problems and the source from which the primate is obtained, must be known and understood by pathologists involved in study design and/or interpretation. The first very important lesson in the "primer" is: there is no such thing as a generic monkey. Brand names (ie, species and subspecies) are important. Several taxonomic groups of primates are used in research including: prosimians, such as galagos and lemurs; New World monkeys, particularily marmosets; Old World monkeys, especially macaques and baboons; and the chimpanzee, an African ape. Differences between taxa are exemplified by the glucocorticoid resistance of New World monkeys compared to Old World monkeys, which results in the requirement for Vitamin D3 and their high circulating levels of steroids such as cortisone and progesterone. Differences in ovarian histology between Old and New World monkeys probably relate to steroid receptor biology as well. There are also variations in disease manifestations, even among closely related primate species such as rhesus and cynomolgus macaques (cynos). For example type D retrovirus infection is accompanied by lymphomas in cynos, but not rhesus. The second important lesson in this "primer" is: "not test article related" does not always mean "normal." Lymphoid nodules in bone marrow or salivary gland, a common background finding in macaques, often signal the presence of type D retrovirus. Other histologic changes and normal anatomic variations may be confusing to individuals not routinely examining primate tissues. The objective of this paper is to familiarize pathologists with the use of primates in research as well as lesions and nonlesions (normal anatomy or physiology) of primates that may influence study design and confound interpretation.

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Section: Gastrointestinal Tractmentioning

confidence: 96%

“…Mast cells are prominent in prosimian tissues. Human herpesvirus simplex 1 can cause fatal disseminated infection in these species, and hepadna-like viruses have recently been identified (118).…”

Section: The Prosimians (Suborder: Prosimii/strepsirrhini Infraordermentioning

confidence: 99%

A Primer of Primate Pathology: Lesions and Nonlesions

Lowenstine

2003

Toxicol Pathol

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“…4A). For example, clusters were observed corresponding to verus subspecies from West Africa (whole genome sequences AB032433, HPBVCG, AB032432, AB032433, AF222323 and Chimp 4), troglodytes from Central Africa (AF222322, Chimp 2 and Louisa), vellerous from Central-West Africa (Osang, AF305327), and a separate clade for (Grethe et al, 2000;Zuckerman et al, 1978;Linnermann, Jr. et al, 1984;Thornton et al, 2001;Worley and Stalis, 2002) Pan troglodytes spp.…”

Section: Chimpanzee Sequencesmentioning

confidence: 99%

Geographic and species association of hepatitis B virus genotypes in non-human primates

et al. 2003

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Infection with hepatitis B virus (HBV) has been detected in human populations throughout the world, as well as in a number of ape species (Pan troglodytes, Gorilla gorilla, gibbons [Nomascus and Hylobates species] and Pongo pygmaeus). To investigate the distribution of naturally occurring HBV infection in these species and other African Old World monkey species (Cercopithecidae), we screened 137 plasma samples from mainly wild caught animals by polymerase chain reaction (PCR) using several of highly conserved primers from the HB surface (HBs) gene, and for HBs antigen (HBsAg) by ELISA. None of the 93 Cercopithecidae screened (6 species) showed PCR or serology evidence for HBV infection; in contrast 2 from 8 chimpanzees and 5 from 22 gibbons were PCR-positive with each set of primers. Complete genome sequences from each of the positive apes were obtained and compared with all previously published complete and surface gene sequences. This extended phylogenetic analysis indicated that HBV variants from orangutans were interspersed by with HBV variants from southerly distributed gibbon species (H. agilis and H. moloch) occupying overlapping or adjacent habitat ranges with orangutans; in contrast, HBV variants from gibbon species in mainland Asia were phylogenetically distinct. A geographical rather than (sub)species association of HBV would account for the distribution of HBV variants in different subspecies of chimpanzees in Africa, and explain the inlier position of the previously described lowland gorilla sequence in the chimpanzee clade. These new findings have a number of implication for understanding the origins and epidemiology of HBV infection in non-human primates.

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“…A HBV-like virus has been described in a black-and-white ruffed lemur (V v variegata), suggesting that some species may have hepadnaviral infections. 23 However, animal models of hepadnavirus-induced HCC (eg, woodchucks, ground squirrels, ducks) typically have viremia associated with tumor development in the majority of affected animals. 21 Another chronic viral infection, HCV, is associated with an increase in liver cancer in humans and possibly chimpanzees, but this infection typically produces chronic inflammation, steatosis, and fibrosis.…”

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confidence: 99%

Spontaneous Hepatocellular Carcinoma in Captive Prosimians

Zadrozny

Williams

Remick³

et al. 2009

Vet Pathol

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Spontaneous hepatocellular carcinoma has been reported as a relatively common neoplasm in prosimians; however, the cause is unknown. To investigate possible pathogenic mechanisms, the authors performed a review of all adult animals from a captive prosimian population that had postmortem examinations over the past 10 years. They performed a detailed histologic evaluation of all suspected proliferative liver lesions and diagnosed hepatocellular carcinoma in 14 of 145 lemurs (9.7%). Affected animals ranged between the ages of 6 and 40 years old. The tumors had an unusually aggressive growth pattern for animal species; metastasis to the lungs or mediastinum was evident in 7 of 14 animals. Thirty-one animals-9 with hepatocellular carcinomas and 22 age-matched controls without hepatic neoplasia-were tested to evaluate the relationship between hepatic iron stores (as well as other trace metals) and the presence of hepatocellular carcinoma. There was no difference between the hepatic iron, copper, or molybdenum in lemurs with hepatocellular carcinoma and those without, suggesting that iron is not a key element in the pathogenesis of liver tumor formation. Analysis of 22 serum samples from animals with and without liver tumors indicated no evidence of active infection with a hepadnavirus, the virus family that includes hepatitis B virus. Hepatitis C virus and aflatoxin B1 were considered as potential causes and ruled out owing to lack of associated histopathologic lesions. In conclusion, hepatocellular neoplasia is relatively common in captive prosimians, although previously suspected etiologies seem unlikely. KeywordsHepadnaviridae, hepatocellular carcinoma, iron, lemur, liver cell adenoma, neoplasms, prosimiansLemurs and lorises are members of the suborder Prosimii, the most primitive members of the Primate family. 15 Lemurs are native to the island of Madagascar, whereas lorises are found in southern Asia. 15 Most of these species are endangered in their natural habitat, and small breeding populations are maintained at various sites around the globe. Our understanding of the general background of neoplastic disease in prosimians is limited to a few publications. 17 In a recent publication, hepatocellular neoplasia was identified as the most common spontaneous neoplasm in prosimians.17 Before this review article, spontaneous hepatic neoplasms were sporadically reported in the literature with only occasional mention of metastasis.Liver tumors in domestic animals are uncommon, representing approximately 1% of overall tumor incidence. Similarly, malignant hepatic neoplasia in anthropoid primates is uncommon. Review of the literature reveals descriptions of fewer than 16 hepatocellular carcinomas (HCCs) and 5 cholangiocarcinomas in nonhuman primates. 16 Only 5 chimpanzees with hepatocellular neoplasia have been reported. Three of the tumors were carcinomas: One occurred in a chimpanzee with chronic hepatitis B virus (HBV), a member of the hepadnaviral family, with concurrent hepatitis D virus, a satellite virus of ...

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Detection of Virus-Like Particles in the Liver of Black and White Ruffed Lemurs With Hepatitis

Cited by 4 publications

References 16 publications

A Primer of Primate Pathology: Lesions and Nonlesions

A Primer of Primate Pathology: Lesions and Nonlesions

Geographic and species association of hepatitis B virus genotypes in non-human primates

Spontaneous Hepatocellular Carcinoma in Captive Prosimians

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