Male CD-1 mice were challenged with a diabetogenic strain (E2) of coxs
ackievirus B4 (CVB4). At 7 weeks, 6 months, and 1 year after inoculati
on, mean histopathologic scores, postprandial blood glucose levels, an
d serum levels of antibody to islet cells were significantly elevated
and mean fasting serum insulin levels significantly reduced in infecte
d mice versus uninfected controls (P < .001 for each). At 7 weeks afte
r infection, viral RNA, but not protein or infectious virus, was demon
strated in the pancreases of most infected mice. The pancreases of 4 o
f 12 and 0 of 10 infected animals were positive for viral RNA at 6 mon
ths and at 1 year after infection, respectively. Interferon-gamma-stim
ulated peritoneal macrophages were cytotoxic to islet cells with and w
ithout sera with high titers of islet cell autoantibody (ICA). Thus, i
slet cell destruction in mice infected with CVB4 strain E2 is associat
ed with chronic islet cell inflammation, elevation of islet cell antib
ody, and prolonged presence of viral RNA in the pancreas. Stimulated p
eritoneal macrophages lyse islet cells directly and by an antibody-dep
endent mechanism.