Molecular genetic identification of isolates of the hepatitis A virus (HAV) from monkeys at Adler Primate Center

Догадов, Д. И.; Korzaya, L I; Karlsen, Anastasia A.; Kyuregyan, Karen K.

doi:10.1111/jmp.12333

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…A high seroprevalence to simian Hepatitis A, which may carry the possibility of zoonotic infection, has been reported in non-human primate colonies. 17 Infection is usually via the faecal–oral route, is self-limiting and asymptomatic. Control usually centres on maintaining appropriate environmental hygiene and the use of personal protective equipment by those in contact with the animals or their environment.…”

Section: Virusesmentioning

confidence: 99%

Revised recommendations for health monitoring of non-human primate colonies (2018): FELASA Working Group Report

Balansard¹,

Cleverley²,

Cutler³

et al. 2019

Lab Anim

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The genetic and biological similarity between non-human primates and humans has ensured the continued use of primates in biomedical research where other species cannot be used. Health-monitoring programmes for non-human primates provide an approach to monitor and control both endemic and incoming agents that may cause zoonotic and anthroponotic disease or interfere with research outcomes. In 1999 FELASA recommendations were published which aimed to provide a harmonized approach to health monitoring programmes for non-human primates. Scientific and technological progress, understanding of non-human primates and evolving microbiology has necessitated a review and replacement of the current recommendations. These new recommendations are aimed at users and breeders of the commonly used non-human primates; Macaca mulatta (Rhesus macaque) and Macaca fascicularis (Cynomolgus macaque). In addition, other species including Callithrix jacchus (Common marmoset) Saimiri sciureus (Squirrel monkey) and others are included. The important and challenging aspects of non-human primate health-monitoring programmes are discussed, including management protocols to maintain and improve health status, health screening strategies and procedures, health reporting and certification. In addition, information is provided on specific micro-organisms and the recommended frequency of testing.

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Section: Virusesmentioning

confidence: 99%

Revised recommendations for health monitoring of non-human primate colonies (2018): FELASA Working Group Report

Balansard¹,

Cleverley²,

Cutler³

et al. 2019

Lab Anim

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“…If, on completion of a study, an unusual pattern of enzyme increases is observed—particularly if an effect appears to worsen following an off-treatment recovery period—then careful follow up investigations for potentially confounding factors, including subclinical infection, should be considered. While rarely specifically investigated, subclinical HAV infection has occasionally been reported in laboratory housed primates, 8 , 9 , 31 including those used for regulatory toxicology studies. 5 Because the liver is the most frequent target organ for drug induced toxicity, 32 , 33 it is particularly likely, that if viral hepatitis was to occur in a toxicology study, the clinical pathology and histopathology findings in animals could be erroneously interpreted (as initially in this study) as test compound-related effects.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] Hepatitis A virus (HAV) is a widely distributed, single stranded RNA picornavirus which infects humans and several primate species. 9 It is highly contagious, transmitted via the oral faecal route, although usually causing only a mild, self-limiting, or subclinical infection. 6 Hepatitis B virus (HBV) infection has also been reported in cynomolgus monkeys from Mauritius, with viral DNA detected in over 40% of liver samples in one study.…”

Section: Introductionmentioning

confidence: 99%

“…Confounding factors may include pre-existing variability in the experimental model, 14,15 uncontrolled environmental influences, [16][17][18] procedural errors, 19 and occasionally, opportunistic or background subclinical infections in experimental models. 9,20,21 This report describes investigations that were prompted by unexpected observations in a toxicology study with a novel, orally-active, small molecule in clinical development for the treatment of a rare genetic disease. The molecule does not have immunomodulatory activity and there is no evidence that the pharmacodynamic activity would modulate susceptibility to infection (pers.…”

Section: Introductionmentioning

confidence: 99%

“…Confounding factors may include pre-existing variability in the experimental model, 14 , 15 uncontrolled environmental influences, 16 - 18 procedural errors, 19 and occasionally, opportunistic or background subclinical infections in experimental models. 9 , 20 , 21 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hepatitis A Virus Infection in Cynomolgus Monkeys Confounds the Safety Evaluation of a Drug Candidate

Powell,

Kapeghian,

Bernal

et al. 2024

Int J Toxicol

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In a 3-month toxicity study in cynomolgus monkeys at a European contract laboratory, animals were infected with HAV, initially resulting in hepatic injury being incorrectly attributed to the test compound. Elevated serum ALT/AST/GLDH (5- to 10-fold) were noted in individual animals from all groups including controls, with no apparent dose, exposure, or time-related relationship. Liver histopathology revealed minimal to slight inflammatory cell accumulation in periportal zones of most animals, and minimal to slight hepatocyte degeneration/necrosis in 10/42 animals from all groups. As these findings were more pronounced in 6 drug-treated animals, including 2/6 in the low dose group, the draft report concluded: “ treatment-related hepatotoxicity at all dose levels precluded determination of a NOAEL.” However, the unusual pattern of hepatotoxicity suggested a factor other than drug exposure might have caused the hepatic effects. Therefore, snap-frozen liver samples were tested for hepatitis viruses using a PCR method. Tests for hepatitis B, C, and E virus were negative; however, 20/42 samples were positive for hepatitis A virus (HAV). Infection was strongly associated with increased serum ALT/GLDH, and/or hepatocyte degeneration/necrosis. Re-evaluation of the study in light of these data concluded that the hepatic injury was not drug-related. A subsequent 6-month toxicology study in HAV-vaccinated cynomolgus monkeys confirmed the absence of hepatotoxicity. Identification of HAV infection supported progression of the drug candidate into later clinical trials. Although rarely investigated, subclinical HAV infection has occasionally been reported in laboratory primates, including those used for toxicology studies and it may be more prevalent than the literature indicates.

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Enteral viral hepatitis in monkeys

Догадов¹,

Kyuregyan²,

Михайлов³

2022

Problems of Virology

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Within the last decade, a large number of viruses genetically related to human hepatitis viruses have been identified in different animal species, including monkeys. Numerous viruses related to human hepatitis A virus (HAV, Picornaviridae: Hepatovirus: Hepatovirus A) were detected in various mammalian species in 2015–2018, predominantly in bats and rodents, but also in shrews, seals and marsupials. Zoonotic hepatitis E virus (HEV, Hepeviridae: Orthohepevirus: Orthohepevirus A) genotypes have been found in wild boars, deer, camels, and rabbits, as well as in non human primates. In addition, viruses that are genetically close to HEV have been described in bats, ferrets, rodents, birds, and fish. Nevertheless, monkeys remain important laboratory animals in HAV and HEV research. The study of spontaneous and experimental infection in these animals is an invaluable source of information about the biology and pathogenesis of these viruses and continues to be an indispensable tool for vaccine and drug testing. The purpose of this literature review was to summarize and analyze published data on the circulation of HAV and HEV among wild and captive primates, as well as the results of experimental studies of HAV and HEV infections in monkeys.

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Molecular genetic identification of isolates of the hepatitis A virus (HAV) from monkeys at Adler Primate Center

Abstract: This study demonstrated the asymptomatic circulation of HAV genotype V among the monkeys at Adler Primate Center, and it indicated the significant genetic diversity within this HAV genotype.

Cited by 6 publications

References 24 publications

Revised recommendations for health monitoring of non-human primate colonies (2018): FELASA Working Group Report

Revised recommendations for health monitoring of non-human primate colonies (2018): FELASA Working Group Report

Hepatitis A Virus Infection in Cynomolgus Monkeys Confounds the Safety Evaluation of a Drug Candidate

Enteral viral hepatitis in monkeys

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