Limits...
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.

Show MeSH

Related in: MedlinePlus

Type-specific antigenicity of the U.S. isolates of RHDV. Liver homogenates from experimentally infected animals were tested by antigen-capture ELISA using type-specific HRP-conjugated monoclonal antibodies (MAb). MAb 1H8 is specific for the original RHDV serotype, MAb 3B12 is specific for the new RHDVa pandemic strain, and MAb 2B4 recognizes a shared epitope. The four U.S. RHDV isolates, Mexico 1989 isolate, an Italian isolate, and Korean isolate were compared in comparison with a control liver homogenate derived from an uninfected rabbit (Normal Liver). All U.S. isolates were recognized by MAb 3B12 as belonging to the RHDVa pandemic strain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2147015&req=5

Figure 5: Type-specific antigenicity of the U.S. isolates of RHDV. Liver homogenates from experimentally infected animals were tested by antigen-capture ELISA using type-specific HRP-conjugated monoclonal antibodies (MAb). MAb 1H8 is specific for the original RHDV serotype, MAb 3B12 is specific for the new RHDVa pandemic strain, and MAb 2B4 recognizes a shared epitope. The four U.S. RHDV isolates, Mexico 1989 isolate, an Italian isolate, and Korean isolate were compared in comparison with a control liver homogenate derived from an uninfected rabbit (Normal Liver). All U.S. isolates were recognized by MAb 3B12 as belonging to the RHDVa pandemic strain.

Mentions: An RHDVa strain-specific antigenic epitope has been previously predicted to reside within residues 344 to 370 in the hypervariable region E of the VP60 capsid protein [35]. Indeed, sequence alignment of the 45 RHDV isolates by CLUSTAL W [48] demonstrated that particular amino acid substitutions within this antigenic epitope are shared among the U.S. isolates and all other RHDVa serotypic variants (Figure 4). While the 344 aa-370 aa RHDVa-specific mutation cluster appeared to be the most significant cluster of type-specific mutations, additional small clusters of RHDVa-specific mutations did appear throughout the VP60 coding region (Additional file 1). To confirm the subtype-specific antigenicity of the remaining three U.S. RHDV isolates, liver homogenates from rabbits experimentally infected with each U.S. isolate were tested by antigen capture ELISA using the original RHDV strain-specific monoclonal antibody 1H8 and the RHDVa strain-specific monoclonal antibody 3B12 (Figure 5). Monocolonal antibody 2B4 was used as a control for the presence of virus and isolates from Italy, Mexico and Korea were tested for comparison to the original RHDV serotype (Figure 5). While all tested virus isolates reacted to the control antibody 2B4, only the U.S. isolates reacted with the RHDVa-specific antibody 3B12 (Figure 5). Likewise, all U.S. virus isolates failed to react with the original RHDV type-specific antibody 1H8. Conversely, isolates from Italy, Mexico and Korea, which fall outside of the RHDVa clade (Figure 2), failed to react with the RHDVa type-specific antibody 3B12 but reacted with the original RHDV type-specific antibody 1H8 (Figure 5).


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)

Type-specific antigenicity of the U.S. isolates of RHDV. Liver homogenates from experimentally infected animals were tested by antigen-capture ELISA using type-specific HRP-conjugated monoclonal antibodies (MAb). MAb 1H8 is specific for the original RHDV serotype, MAb 3B12 is specific for the new RHDVa pandemic strain, and MAb 2B4 recognizes a shared epitope. The four U.S. RHDV isolates, Mexico 1989 isolate, an Italian isolate, and Korean isolate were compared in comparison with a control liver homogenate derived from an uninfected rabbit (Normal Liver). All U.S. isolates were recognized by MAb 3B12 as belonging to the RHDVa pandemic strain.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Type-specific antigenicity of the U.S. isolates of RHDV. Liver homogenates from experimentally infected animals were tested by antigen-capture ELISA using type-specific HRP-conjugated monoclonal antibodies (MAb). MAb 1H8 is specific for the original RHDV serotype, MAb 3B12 is specific for the new RHDVa pandemic strain, and MAb 2B4 recognizes a shared epitope. The four U.S. RHDV isolates, Mexico 1989 isolate, an Italian isolate, and Korean isolate were compared in comparison with a control liver homogenate derived from an uninfected rabbit (Normal Liver). All U.S. isolates were recognized by MAb 3B12 as belonging to the RHDVa pandemic strain.
Mentions: An RHDVa strain-specific antigenic epitope has been previously predicted to reside within residues 344 to 370 in the hypervariable region E of the VP60 capsid protein [35]. Indeed, sequence alignment of the 45 RHDV isolates by CLUSTAL W [48] demonstrated that particular amino acid substitutions within this antigenic epitope are shared among the U.S. isolates and all other RHDVa serotypic variants (Figure 4). While the 344 aa-370 aa RHDVa-specific mutation cluster appeared to be the most significant cluster of type-specific mutations, additional small clusters of RHDVa-specific mutations did appear throughout the VP60 coding region (Additional file 1). To confirm the subtype-specific antigenicity of the remaining three U.S. RHDV isolates, liver homogenates from rabbits experimentally infected with each U.S. isolate were tested by antigen capture ELISA using the original RHDV strain-specific monoclonal antibody 1H8 and the RHDVa strain-specific monoclonal antibody 3B12 (Figure 5). Monocolonal antibody 2B4 was used as a control for the presence of virus and isolates from Italy, Mexico and Korea were tested for comparison to the original RHDV serotype (Figure 5). While all tested virus isolates reacted to the control antibody 2B4, only the U.S. isolates reacted with the RHDVa-specific antibody 3B12 (Figure 5). Likewise, all U.S. virus isolates failed to react with the original RHDV type-specific antibody 1H8. Conversely, isolates from Italy, Mexico and Korea, which fall outside of the RHDVa clade (Figure 2), failed to react with the RHDVa type-specific antibody 3B12 but reacted with the original RHDV type-specific antibody 1H8 (Figure 5).

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