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A pandemic strain of calicivirus threatens rabbit industries in the Americas.

McIntosh MT, Behan SC, Mohamed FM, Lu Z, Moran KE, Burrage TG, Neilan JG, Ward GB, Botti G, Capucci L, Metwally SA - Virol. J. (2007)

Bottom Line: Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage.Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype.Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat.

View Article: PubMed Central - HTML - PubMed

Affiliation: Foreign Animal Disease Diagnostic Laboratory, Animal and Plant Health Inspection Services, United States Department of Agriculture, Plum Island Animal Disease Center, P,O, Box 848, Greenport, NY 11944, USA. michael.t.mcintosh@aphis.usda.gov

ABSTRACT
Rabbit Hemorrhagic Disease (RHD) is a severe acute viral disease specifically affecting the European rabbit Oryctolagus cuniculus. As the European rabbit is the predominant species of domestic rabbit throughout the world, RHD contributes towards significant losses to rabbit farming industries and endangers wild populations of rabbits in Europe and other predatory animals in Europe that depend upon rabbits as a food source. Rabbit Hemorrhagic Disease virus (RHDV) - a Lagovirus belonging to the family Caliciviridae is the etiological agent of RHD. Typically, RHD presents with sudden death in 70% to 95% of infected animals. There have been four separate incursions of RHDV in the USA, the most recent of which occurred in the state of Indiana in June of 2005. Animal inoculation studies confirmed the pathogenicity of the Indiana 2005 isolate, which caused acute death and pathological changes characterized by acute diffuse severe liver necrosis and pulmonary hemorrhages. Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage. All of the USA isolates clustered with RHDV genomes from China, and phylogenetic analysis of the major capsid protein (VP60) revealed that they were related to a pandemic antigenic variant strain known as RHDVa. Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype. Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat.

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Histopathology and cytopathology associated with IN-05 RHDVa infection. A. A liver section from one of the fatally infected rabbits (day 2 post infection) is shown (H&E stain, 40× objective). Note the acute hepatocellular necrosis characterized by destruction and disassociation of hepatocytes, loss of cellular organization, and evidence of acidophilic bodies (white arrow head), karyorrhexis (white arrow), and necrotic or apoptotic hepatocytes (black arrow head). B. A liver section from the surviving infected rabbit (day 21 post infection) exhibited normal liver morphology (H&E staine, 40× objective). C. Transmission electron micrograph showing the ultrastructure of a hepatocyte from a fatally infected rabbit revealed the presence of 26.5 nm +/- 1.9 diameter viral particles with morphology characteristic of caliciviruses. D. An example of ultrastructural changes to a hepatocyte from one of the fatally infected rabbits. Note the margination of chromatin (Ch) in the nucleus (Nu), and disruption of cristae in mitochondria (Mt). Often, an abnormal condensation of the endoplasmic reticulum (ER) was observed. The inset shows an abnormally dense reticular network.
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Figure 1: Histopathology and cytopathology associated with IN-05 RHDVa infection. A. A liver section from one of the fatally infected rabbits (day 2 post infection) is shown (H&E stain, 40× objective). Note the acute hepatocellular necrosis characterized by destruction and disassociation of hepatocytes, loss of cellular organization, and evidence of acidophilic bodies (white arrow head), karyorrhexis (white arrow), and necrotic or apoptotic hepatocytes (black arrow head). B. A liver section from the surviving infected rabbit (day 21 post infection) exhibited normal liver morphology (H&E staine, 40× objective). C. Transmission electron micrograph showing the ultrastructure of a hepatocyte from a fatally infected rabbit revealed the presence of 26.5 nm +/- 1.9 diameter viral particles with morphology characteristic of caliciviruses. D. An example of ultrastructural changes to a hepatocyte from one of the fatally infected rabbits. Note the margination of chromatin (Ch) in the nucleus (Nu), and disruption of cristae in mitochondria (Mt). Often, an abnormal condensation of the endoplasmic reticulum (ER) was observed. The inset shows an abnormally dense reticular network.

Mentions: RHDV is known to replicate in the liver, which results in severe liver necrosis and terminally disseminated intravascular coagulation [7,43-45]. Homogenates prepared from livers of the two fatally infected animals tested positive for VP60 capsid antigen, while the liver homogenate from the surviving animal, taken on day 21 post infection, was negative for viral capsid antigen by antigen capture ELISA (Table 1). Animals that succumb to RHD typically display splenomegaly, a pale necrotic liver, and a multitude of infarcts and hemorrhages throughout the lungs. Upon necropsy, livers of the two rabbits that had died during the study were pale, and on histopathology displayed multifocal to coalescing acute severe hepatic necrosis (Figure 1A). The distribution of necrosis was mostly periportal extending towards the midzonal areas. Necrotic areas were characterized by disassociation of the hepatic cords, cellular swelling, hypereosinophilia and hepatocellular vacuolar changes (Figure 1A). Hepatocellular changes were characterized by pyknosis, karyorrhexis and karyolysis. Some of the degenerating hepatocytes contained intracytoplasmic acidophilic bodies. Infiltration by inflammatory cells was minimal and consisted mainly of neutrophils. In contrast, liver tissue from the surviving rabbit showed no evidence of necrosis or hemorrhage (Figure 1B). Lungs from the fatally infected rabbits showed pulmonary congestion and hemorrhage, and spleens were characterized by diffuse splenic congestion and mild lymphoid hyperplasia with lymphocytic apoptosis.


A pandemic strain of calicivirus threatens rabbit industries in the Americas.

McIntosh MT, Behan SC, Mohamed FM, Lu Z, Moran KE, Burrage TG, Neilan JG, Ward GB, Botti G, Capucci L, Metwally SA - Virol. J. (2007)

Histopathology and cytopathology associated with IN-05 RHDVa infection. A. A liver section from one of the fatally infected rabbits (day 2 post infection) is shown (H&E stain, 40× objective). Note the acute hepatocellular necrosis characterized by destruction and disassociation of hepatocytes, loss of cellular organization, and evidence of acidophilic bodies (white arrow head), karyorrhexis (white arrow), and necrotic or apoptotic hepatocytes (black arrow head). B. A liver section from the surviving infected rabbit (day 21 post infection) exhibited normal liver morphology (H&E staine, 40× objective). C. Transmission electron micrograph showing the ultrastructure of a hepatocyte from a fatally infected rabbit revealed the presence of 26.5 nm +/- 1.9 diameter viral particles with morphology characteristic of caliciviruses. D. An example of ultrastructural changes to a hepatocyte from one of the fatally infected rabbits. Note the margination of chromatin (Ch) in the nucleus (Nu), and disruption of cristae in mitochondria (Mt). Often, an abnormal condensation of the endoplasmic reticulum (ER) was observed. The inset shows an abnormally dense reticular network.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2147015&req=5

Figure 1: Histopathology and cytopathology associated with IN-05 RHDVa infection. A. A liver section from one of the fatally infected rabbits (day 2 post infection) is shown (H&E stain, 40× objective). Note the acute hepatocellular necrosis characterized by destruction and disassociation of hepatocytes, loss of cellular organization, and evidence of acidophilic bodies (white arrow head), karyorrhexis (white arrow), and necrotic or apoptotic hepatocytes (black arrow head). B. A liver section from the surviving infected rabbit (day 21 post infection) exhibited normal liver morphology (H&E staine, 40× objective). C. Transmission electron micrograph showing the ultrastructure of a hepatocyte from a fatally infected rabbit revealed the presence of 26.5 nm +/- 1.9 diameter viral particles with morphology characteristic of caliciviruses. D. An example of ultrastructural changes to a hepatocyte from one of the fatally infected rabbits. Note the margination of chromatin (Ch) in the nucleus (Nu), and disruption of cristae in mitochondria (Mt). Often, an abnormal condensation of the endoplasmic reticulum (ER) was observed. The inset shows an abnormally dense reticular network.
Mentions: RHDV is known to replicate in the liver, which results in severe liver necrosis and terminally disseminated intravascular coagulation [7,43-45]. Homogenates prepared from livers of the two fatally infected animals tested positive for VP60 capsid antigen, while the liver homogenate from the surviving animal, taken on day 21 post infection, was negative for viral capsid antigen by antigen capture ELISA (Table 1). Animals that succumb to RHD typically display splenomegaly, a pale necrotic liver, and a multitude of infarcts and hemorrhages throughout the lungs. Upon necropsy, livers of the two rabbits that had died during the study were pale, and on histopathology displayed multifocal to coalescing acute severe hepatic necrosis (Figure 1A). The distribution of necrosis was mostly periportal extending towards the midzonal areas. Necrotic areas were characterized by disassociation of the hepatic cords, cellular swelling, hypereosinophilia and hepatocellular vacuolar changes (Figure 1A). Hepatocellular changes were characterized by pyknosis, karyorrhexis and karyolysis. Some of the degenerating hepatocytes contained intracytoplasmic acidophilic bodies. Infiltration by inflammatory cells was minimal and consisted mainly of neutrophils. In contrast, liver tissue from the surviving rabbit showed no evidence of necrosis or hemorrhage (Figure 1B). Lungs from the fatally infected rabbits showed pulmonary congestion and hemorrhage, and spleens were characterized by diffuse splenic congestion and mild lymphoid hyperplasia with lymphocytic apoptosis.

Bottom Line: Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage.Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype.Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat.

View Article: PubMed Central - HTML - PubMed

Affiliation: Foreign Animal Disease Diagnostic Laboratory, Animal and Plant Health Inspection Services, United States Department of Agriculture, Plum Island Animal Disease Center, P,O, Box 848, Greenport, NY 11944, USA. michael.t.mcintosh@aphis.usda.gov

ABSTRACT
Rabbit Hemorrhagic Disease (RHD) is a severe acute viral disease specifically affecting the European rabbit Oryctolagus cuniculus. As the European rabbit is the predominant species of domestic rabbit throughout the world, RHD contributes towards significant losses to rabbit farming industries and endangers wild populations of rabbits in Europe and other predatory animals in Europe that depend upon rabbits as a food source. Rabbit Hemorrhagic Disease virus (RHDV) - a Lagovirus belonging to the family Caliciviridae is the etiological agent of RHD. Typically, RHD presents with sudden death in 70% to 95% of infected animals. There have been four separate incursions of RHDV in the USA, the most recent of which occurred in the state of Indiana in June of 2005. Animal inoculation studies confirmed the pathogenicity of the Indiana 2005 isolate, which caused acute death and pathological changes characterized by acute diffuse severe liver necrosis and pulmonary hemorrhages. Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage. All of the USA isolates clustered with RHDV genomes from China, and phylogenetic analysis of the major capsid protein (VP60) revealed that they were related to a pandemic antigenic variant strain known as RHDVa. Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype. Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat.

Show MeSH
Related in: MedlinePlus