Molecular Determinants of Disease in Coxsackievirus B1 Murine Infection

JAVIER O. CIFUENTE; MARIA F. FERRER; CAROLINA JAQUENOD DE GIUSTI; WEN-CHAO SONG; VICTOR ROMANOWSKI; SUSAN L. HAFENSTEIN; RICARDO M. GOMEZ

JOURNAL OF MEDICAL VIROLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2011 vol. 83 p. 1571 - 1581

0146-6615

To understand better how different genomic regions may confer pathogenicity for the coxsackievirus B (CVB), two intratypic CVB1 variants, and a number of recombinant viruseswere studied. Sequencing analysis showed 23 nucleotide changes between the parental non-pathogenic CVB1N and the pathogenic CVB1Nm. Mutations present in CVB1Nm weremore conserved than those in CVB1N when compared to other CVB sequences. Inoculationin C3H/HeJ mice showed that the P1 region is critical for pathogenicity in murine pancreasand heart. The molecular determinants of disease for these organs partially overlap. SeveralP1 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 issu.