Secondary heterotypic versus homotypic infection by Coxsackie B group viruses: Impact on early and late histopathological lesions and virus genome prominence

The impact of prior exposure to a different or identical strain of Coxsacki evirus B (CVB) on murine CVB myocarditis was studied using a susceptible mu rine host (A/J[H-2(a)]) and myocarditic CVB3 or avirulent CVB2 as primary o r secondary infectants. The effects of secondary heterotypic infection (CVB 2 followed by CVB3) and homotypic infection (CVB3 followed by CVB3) 28 days after primary inoculation, versus CVB2 or CVB3 alone, on injury and viral genomic replication, both early (day 7) and late (days 28 and 56), were eva luated. After the primary infection by CVB2, trivial viral RNA was present in the heart and other organs, and a substantial positivity was observed wi th CVB3 infection. Seven days after secondary heterotypic (CVB2-CVB3) infec tion, the quantity of CVB genome in heart, pancreas, liver, and spleen was increased compared with the virus genome in the CVB3-CVB3 group and in the group with primary CVB3 infection alone. This phenomenon was seen in the he art and spleen up to day 28 postsecondary infection. Tissue inflammation an d necrosis in heart and pancreas were prominent 7 days postsecondary infect ion with CVB2-CVB3 and correlated well with an increased quantity of CVB ge nome. Virus genome was present in heart and spleen 28 days after CVB3 infec tion alone. Serum CVB3 neutralization titer was increased to 1:128 in CVB2- CVB3 group at days 7 and 28 postsecondary infection, and serum completely n eutralized cytopathological effects of CVB3 in the CVB3-CVB3 group at day 7 and 28 postsecondary infection. Our results indicate that secondary hetero typic infection by CVB causes increased injury, inflammation, and CVB repli cation in target organs such as the heart and pancreas, as well as in immun e compartments like the spleen. Compared with CVB3 alone, the intense infla mmatory infiltrate in the CVB2-CVB3 group is as not due solely to postviral sensitization of the immune system, but rather to the inability of the hos t to eradicate the virus. (C) 1999 by Elsevier Science Inc.