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 Coxsackievirus B (CVB) on murine CVB myocarditis was studied using a susceptible murine host (A/J[H-2a]) and myocarditic CVB3 or avirulent CVB2 as primary or secondary infectants. The effects of secondary heterotypic infection (CVB2 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 evaluated. After the primary infection by CVB2, trivial viral RNA was present in the heart and other organs, and a substantial positivity was observed with CVB3 infection. Seven days after secondary heterotypic (CVB2-CVB3) infection, 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 heart and spleen up to day 28 postsecondary infection. Tissue inflammation and necrosis in heart and pancreas were prominent 7 days postsecondary infection with CVB2-CVB3 and correlated well with an increased quantity of CVB genome. Virus genome was present in heart and spleen 28 days after CVB3 infection alone. Serum CVB3 neutralization titer was increased to 1:128 in CVB2-CVB3 group at days 7 and 28 postsecondary infection, and serum completely neutralized cytopathological effects of CVB3 in the CVB3-CVB3 group at day 7 and 28 postsecondary infection. Our results indicate that secondary heterotypic infection by CVB causes increased injury, inflammation, and CVB replication in target organs such as the heart and pancreas, as well as in immune compartments like the spleen. Compared with CVB3 alone, the intense inflammatory infiltriate in the CVB2-CVB3 group is as not due solely to postviral sensitization of the immune system, but rather to the inability of the host to eradicate the virus.
Yu
J Z
JZ
Department of Pathology and Laboratory Medicine, St Paul's Hospital-University of British Columbia, Vancouver, Canada.
Wilson
J E
JE
Wood
S M
SM
Kandolf
R
R
Klingel
K
K
Yang
D
D
McManus
B M
BM
D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis; D003384:Coxsackievirus Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology; D003588:Cytopathogenic Effect, Viral; D029822:Enterovirus B, Human / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D016679:Genome, Viral; D006321:Heart / Q000821:virology*; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009205:Myocarditis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000473:pathology*; D012367:RNA, Viral / Q000032:analysis; D013154:Spleen / Q000473:pathology / Q000821:virology; D014779:Virus Replication
D000910:Antibodies, Heterophile; D000914:Antibodies, Viral; D012367:RNA, Viral