N. P. DEPASQUALE AND GEORGE E. BURGH 
947 
COXSACKIEVIRUS B4 VALVULITIS 
(Mitral Valve) 
CYN0M0L6US MONKEY 
178 Days after I.V. Inoculation Monkey #6 
Figure 3. — Photograph showing verrucous lesion of 
the mitral valve associated with thickening of the 
valve in a cynomolgus monkey. The animal was 
killed 178 days after inoculation with coxsackievirus 
B, (Am. Heart J. 71:678, 1966). 
Direct fluorescent antibody staining was car- 
ried out in 3 of the virus inoculated animals and 
in 1 control animal. Viral antigen was identified 
in valve tissue from the 3 virus-inoculated ani- 
mals whereas valve tissue from the control ani- 
mal was negative for viral antigen. 
DISCUSSION 
Physicians are often willing to attribute non- 
congenital chronic valvular disease to rheu- 
matic fever even in the absence of a history of 
rheumatic carditis. Although occult or subclini- 
cal rheumatic fever does occur, it is unreason- 
I able to assume that all instances of chronic val- 
vular disease would occur secondarily to such 
unestablished entities. 
Although clinicians and pathologists have not 
recognized acute and chronic viral valvulitis, 
valvular lesions have been produced in experi- 
mental animals by a variety of viruses. Pearce 
demonstrated that inoculation of rabbits with 
j Virus III resulted in valvular lesions associated 
, with infiltration of valve tissue with mononu- 
lear cells containing characteristic inclusion 
bodies.^ Pearce also found that vaccinia, pseudo- 
rabies and inflammatory fibroma viruses pro- 
duced valvular lesions in acacia-prepared 
animals.*''' Kilham, Mason, and Davies pro- 
duced endocarditis in African mongooses using 
the Mengo strain of encephalomyocarditis 
virus.^ Lou, Wenner, and Kamitsuka found 
mural endocarditis in 4 and mitral valvulitis in 
2 of 9 cynomolgus monkeys inoculated with 
group B4 coxsackievirus.® 
The studies described in this paper demon- 
etrate that group B4 coxsackieviral infection is 
often associated with acute valvulitis and mural 
endocarditis in mice. Furthermore, chronic ex- 
periments in cynomolgus monkeys demon- 
strated that viral infection may result in gross 
and microscopic valvular lesions which are 
strikingly similar to those of rheumatic valvuli- 
tis including fibrotic thickening of the valve 
leaflets, commissural adhesions, and shortening 
and thickening of the papillary muscles. In ad- 
dition, immunofluorescent Bi coxsackievirus 
antigen was found in valves as well as in the 
COXSACKIEVIRUS B4 VALVULITIS 
(Mitral Valve) 
CYNOMOLGUS MONKEY 
200 Days after I. V. Inoculation Monkey ^9 
Figure 4. — Photograph showing fibrosis and thickening 
of the mitral valve with commissural adhesions 
(stenosis) and thickening and shortening of the chor- 
dae tendineae in a cynomolgus monkey. The animal 
was killed 200 days after inoculation with coxsackie- 
virus B4 (Am. Heart J. 71:678, 1966). 
