Spontaneous T/NK-cell Lymphoma associated with Simian Lymphocryptovirus in a Japanese Macaque (Macaca fuscata)

Hirata, Akihiro; Tachikawa, Yoshiharu; Hashimoto, Kazumune; Sakai, Hiroki; Kaneko, Akihisa; Suzuki, Juri; Eguchi, Katsuyuki; Shigematsu, Kazuto; Nikami, Hideki; Yanai, Tokuma

doi:10.1016/j.jcpa.2012.05.001

Cited by 3 publications

(7 citation statements)

References 12 publications

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“…Case No. 1 has been described in a case report, 16 but additional analysis was performed in the present study.…”

Section: Methodsmentioning

confidence: 73%

“…Necropsies were performed at each facility after death (case Nos. [2][3][4][5] 16 but additional analysis was performed in the present study.…”

Section: Animalsmentioning

confidence: 99%

“…4,6,14,20,24,26 However, the previously reported cases of lymphoma in Japanese macaques exhibited a T/NK-cell phenotype with EBER-positive signals, 16,29 suggesting the possibility that Japanese macaque LCVs have tropisms for T cells and/or NK cells. Therefore, further investigations are required to characterize the immunophenotypes of lymphomas and to define the cell tropism of LCVs in Japanese macaques.…”

mentioning

confidence: 99%

“…Meanwhile, the oncogenic potential of macaque LCVs has been suspected in prior case reports. Although there are only 2 reports of lymphomas in Japanese macaques, positive signals for EBV-encoded small RNA (EBER) in situ hybridization were detected in the tumor cells of both animals, 16,29 suggesting that lymphoma could be associated with macaque LCV infection. However, it remains unclear how frequently macaque LCV infection is present in lymphomas of Japanese macaques.…”

mentioning

confidence: 99%

“…However, except for rhesus macaques ( Macaca mulatta ), 25 it has been difficult to detect EBER homolog transcripts of macaque LCVs by in situ hybridization using specific probes due to a lack of available sequence data of EBER homologs. We previously demonstrated that the application of peptide nucleic acid probes for EBER is useful for detecting macaque LCVs in Japanese macaques, 16 which prompted us to further investigate the presence of LCVs in lymphomas in Japanese macaques. Besides in situ hybridization for EBER, immunohistochemistry is used to detect EBV-related antigens, including EBV-encoded nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1).…”

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confidence: 99%

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Characterization of Spontaneous Malignant Lymphomas in Japanese Macaques (Macaca fuscata)

et al. 2014

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Lymphomas are common spontaneous tumors in nonhuman primates but remain poorly characterized in Japanese macaques (Macaca fuscata). This study examined 5 cases of spontaneous malignant lymphoma in Japanese macaques, focusing on the immunophenotypes and presence of simian lymphocryptoviruses, which are Epstein-Barr virus-related herpesviruses in nonhuman primates. The macaques with lymphoma were 5 to 28 years old, indicating that lymphomas develop over a wide age range. The common macroscopic findings were splenomegaly and enlargement of lymph nodes. Histologic and immunohistochemical analyses revealed that all cases were non-Hodgkin type and exhibited a T-cell phenotype, positive for CD3 but negative for CD20 and CD79a. The lymphomas exhibited diverse cellular morphologies and were subdivided into 3 types according to the World Health Organization classification. These included 3 cases of peripheral T-cell lymphoma, not otherwise specified; 1 case of T-cell prolymphocytic leukemia; and 1 case of an unclassifiable T-cell lymphoma. Positive signals were detected by in situ hybridization in 2 of the 4 examined cases using probes for the Epstein-Barr virus-encoded small RNA (EBER). Furthermore, the presence of M. fuscata lymphocryptovirus 2, a macaque homolog of Epstein-Barr virus, was demonstrated in EBER-positive cases by polymerase chain reaction amplification followed by direct sequencing. Immunohistochemistry using antibody to the Epstein-Barr virus-encoded nuclear antigen 2 was negative, even in the EBER-positive cases. The present study suggests that T-cell lymphoma is more common than B-cell lymphoma in Japanese macaques and that M. fuscata lymphocryptovirus 2 is present in some cases.

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“…Case No. 1 has been described in a case report, 16 but additional analysis was performed in the present study.…”

Section: Methodsmentioning

confidence: 73%

“…Necropsies were performed at each facility after death (case Nos. [2][3][4][5] 16 but additional analysis was performed in the present study.…”

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of Spontaneous Malignant Lymphomas in Japanese Macaques (Macaca fuscata)

et al. 2014

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Mountain gorilla lymphocryptovirus has Epstein-Barr virus-like epidemiology and pathology in infants

Evans

Lowenstine

Gilardi

et al. 2017

Sci Rep

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Epstein-Barr virus (EBV) infects greater than 90% of humans, is recognized as a significant comorbidity with HIV/AIDS, and is an etiologic agent for some human cancers. The critically endangered mountain gorilla population was suspected of infection with an EBV-like virus based on serology and infant histopathology similar to pulmonary reactive lymphoid hyperplasia (PRLH), a condition associated with EBV in HIV-infected children. To further examine the presence of EBV or an EBV-like virus in mountain gorillas, we conducted the first population-wide survey of oral samples for an EBV-like virus in a nonhuman great ape. We discovered that mountain gorillas are widely infected (n = 143/332) with a specific strain of lymphocryptovirus 1 (GbbLCV-1). Fifty-two percent of infant mountain gorillas were orally shedding GbbLCV-1, suggesting primary infection during this stage of life, similar to what is seen in humans in less developed countries. We then identified GbbLCV-1 in post-mortem infant lung tissues demonstrating histopathological lesions consistent with PRLH, suggesting primary infection with GbbLCV-1 is associated with PRLH in infants. Together, our findings demonstrate that mountain gorilla’s infection with GbbLCV-1 could provide valuable information for human disease in a natural great ape setting and have potential conservation implications in this critically endangered species.

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Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Ohta

2023

J Toxicol Pathol

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Nonhuman primates (NHPs), which have many advantages in scientific research and are often the only relevant animals to use in assessing the safety profiles and biological or pharmacological effects of drug candidates, including biologics. In scientific or developmental experiments, the immune systems of animals can be spontaneously compromised possibly due to background infection, experimental procedure-associated stress, poor physical condition, or intended or unintended mechanisms of action of test articles. Under these circumstances, background, incidental, or opportunistic infections can seriously can significantly complicate the interpretation of research results and findings and consequently affect experimental conclusions. Pathologists and toxicologists must understand the clinical manifestations and pathologic features of infectious diseases and the effects of these diseases on animal physiology and experimental results in addition to the spectrum of infectious diseases in healthy NHP colonies. This review provides an overview of the clinical and pathologic characteristics of common viral, bacterial, fungal, and parasitic infectious diseases in NHPs, especially macaque monkeys, as well as methods for definitive diagnosis of these diseases. Opportunistic infections that can occur in the laboratory setting have also been addressed in this review with examples of cases of infection disease manifestation that was observed or influenced during safety assessment studies or under experimental conditions.

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Spontaneous T/NK-cell Lymphoma associated with Simian Lymphocryptovirus in a Japanese Macaque (Macaca fuscata)

Cited by 3 publications

References 12 publications

Characterization of Spontaneous Malignant Lymphomas in Japanese Macaques (Macaca fuscata)

Characterization of Spontaneous Malignant Lymphomas in Japanese Macaques (Macaca fuscata)

Mountain gorilla lymphocryptovirus has Epstein-Barr virus-like epidemiology and pathology in infants

Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

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