Nucleotide sequence of an attenuated mutant of coxsackievirus B3 compared with the cardiovirulent wildtype: assessment of candidate mutations by analysis of a revertant to cardiovirulence.

Background: Coxsackievirus B3 (CVB3) causes myocarditis in the SWR (H2q) mouse model and persistence of CVB3 in myocardium disposes to the development of dilated cardiomyopathy. An attenuated strain of CVB3 has been isolated, sequenced and several candidate mutations for attenuation identified. Derivation of a revertant to cardiovirulence allows the significance of these mutations to be assessed.

Coxsackievirus B3-induced myocarditis. Characterization of stable attenuated variants that protect against infection with the cardiovirulent wild-type strain.

Coxsackievirus B3 (CVB3) is the enterovirus most frequently involved in human myocarditis or dilated cardiomyopathy. Attenuated variants were derived from a cardiovirulent CVB3 reactivated from a sequenced, full-length cDNA clone. The prophylactic potential of these variants was assessed in SWR/Ola (H-2q) mice.

A single amino acid substitution in the capsid protein VP1 of coxsackievirus B3 (CVB3) alters plaque phenotype in Vero cells but not cardiovirulence in a mouse model.

We previously described a large plaque attenuant (p14V-1) derived from a cardiovirulent Coxsackievirus B3 (CVB3) and showed that there were no major determinants of either attenuation or plaque phenotype in the 5' nontranslated region (5'NTR). Part of the region encoding the last 124 amino acids of VP3 and the first 106 amino acids of VP1 of the attenuant was then sequenced and compared to the wild-type. Three nucleotide changes were found in the VP1 coding region: a silent single base change at nucleotide position 2467 (C to U) and a double-base change at position 2690-1 (AA to GT), which leads to a change from lysine to serine at amino acid position 80.

The immune response to and expression of cross-reactive retroviral gag sequences in autoimmune disease.

To examine the immune response to retroviral gag sequences in autoimmune disease, we measured antibody levels to synthetic peptides representing the major epitopes on HTLV-1 p19 gag and a homologous sequence on the endogenous retrovirus, HRES-1, in sera from 121 patients with autoimmune disease and 52 healthy controls. In the absence of HTLV-1 antibodies, using a conventional diagnostic assay, significantly elevated levels of antibodies to the HTLV-1 peptide were found in 23% of multiple sclerosis and 20% of anti-Sm antibody positive systemic lupus erythematosus patients. Elevated antibody levels to HRES-1 were found in 32% of Sjögren's syndrome and 19% of multiple sclerosis patients.