Abstract
To understand better how different genomic regions may confer pathogenicity for the coxsackievirus B (CVB), two intratypic CVB1 variants, and a number of recombinant viruses were studied. Sequencing analysis showed 23 nucleotide changes between the parental non-pathogenic CVB1N and the pathogenic CVB1Nm. Mutations present in CVB1Nm were more conserved than those in CVB1N when compared to other CVB sequences. Inoculation in C3H/HeJ mice showed that the P1 region is critical for pathogenicity in murine pancreas and heart. The molecular determinants of disease for these organs partially overlap. Several P1 region amino acid differences appear to be located in the decay-accelerating factor (DAF) footprint CVBs. CVB1N and CVB1Nm interacted with human CAR, but only CVB1N seemed to interact with human DAF, as determined using soluble receptors in a plaque-reduction assay. However, the murine homolog Daf-1 did not interact with any virus assessed by hemagglutination. The results of this study suggest that an unknown receptor interaction with the virus play an important role in the pathogenicity of CVB1Nm. Further in vivo studies may clarify this issue.
Highlights
Coxsackieviruses (CVs) belong to the genus Enterovirus within the Picornaviridae family [Pallansch and Roos, 2001]
CVB1N was inoculated into severe combined immunodeficiency (SCID) mice and viral isolations were obtained from various tissues
The frequency of occurrence was determined according to the identity of the residue of interest, based on whether the identity was that found in CVB1N, CVB1Nm or other virus
Summary
Coxsackieviruses (CVs) belong to the genus Enterovirus within the Picornaviridae family [Pallansch and Roos, 2001]. Soon after their initial isolation, CVs were divided into subgroups A and B (CVA and CVB) according to their pathogenicity in suckling mice [Hyypia et al, 1993]. Based on its molecular characteristics, the CVB subgroup, which includes six serotypes, is currently classified as human enterovirus B [Fauquet et al, 2005; Oberste, 2008]. CVB1 was the predominant enterovirus isolated in the USA among young infants with severe disease in 2007 [MMRW, 2008; Wikswo et al, 2009] and continued to be the most common serotype detected in 2008 [MRRW, 2010]
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