Chimpanzees in Biomedical and Behavioral Research by National Research Council

Author:National Research Council
Language: eng
Format: epub
Tags: Biology and Life Sciences: Laboratory Animal Research, Health and Medicine: Public Health and Prevention, Agriculture: Animal Health and Nutrition
ISBN: 9780309220422
Publisher: The National Academies Press
Published: 2012-11-17T00:00:00+00:00

Enteric Hepatitis Viruses

HAV and HEV cause acute hepatitis and self-limited infection in humans and chimpanzees. Although liver disease may be somewhat milder in chimpanzees, the kinetics and magnitude of virus replication, onset of liver disease, and histopathological changes in the liver are similar to those in HAV-infected humans (Dienstag et al., 1975, 1976). The course of HEV infection in chimpanzees is variable, ranging from low viremia with no obvious liver disease to high viremia with biochemical and histological evidence of hepatitis (Li et al., 2006; McCaustland et al., 2000). This may be similar to the spectrum of disease in HEV-infected humans (McCaustland et al., 2000). HAV and HEV infections are preventable by vaccination. The efficacy of a subunit HEV vaccine was ap- proximately 90 percent in two large human trials in Nepal and China, but there is uncertainty about the durability of protective immunity as currently formulated and how (or if) it will be deployed where needed (Shrestha et al., 2007; Wedemeyer and Pischke, 2011; Zhu et al., 2010). Thus it is likely that endemic and epidemic HEV will remain a cause of serious liver disease in developing countries (Aggarwal, 2011). HEV immunity and pathogenesis are still very poorly understood (Aggarwal, 2011). For HAV, socioeconomic development accompanied by improved sanitation and opportunity for vaccination has changed epidemiology in regions where the virus is still endemic, as illustrated by a recent outbreak in South Korea (Kim and Lee, 2010; Kwon, 2009). Under these circumstances, HAV infection shifts from the first to the second and third decades of life with an associated increase in the severity of disease. This situation has highlighted a gap in knowledge about mechanisms of immunity and hepatocellular injury caused by HAV. Very recent studies in chimpanzees provided insight into patterns of innate immunity and host gene expression immediately after infection with HAV and HEV, with the goal of understanding the pathogenesis of these infections and how they compare to responses elicited by HCV that often establishes a persistent infection (Lanford et al., 2011; Yu et al., 2010a). Follow up studies of adaptive immunity to these viruses in animals should be anticipated. Similar studies in humans will be difficult, if not impossible, because infections with these small RNA viruses are often not symptomatic for several weeks and access to liver may be challenging as there is typically no medical need for liver biopsy.

HBV Worldwide, approximately 500 million people are infected with HBV. Hepadnaviruses are widespread in nature and chimpanzees do harbor indigenous strains of HBV that can be distinguished from human viruses based on genomic signatures despite overall identity of about 90 percent (Barker et al., 1975a, 1975b; Dienstag et al., 1976; Guidotti et al., 1999; Hu et al., 2000; Rizzetto et al., 1981). Chimpanzees are nevertheless highly susceptible to challenge with human HBV. Chimpanzees develop persistent and resolved infections after challenge with the virus (Barker et al., 1975a, 1975b). The incubation period preceding symptoms is long and biochemical evidence of acute hepatitis is associated with parenchymal inflammation, as in man.

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