Human enterovirus in the gastrocnemius of patients with peripheral arterial disease.
BACKGROUND
Peripheral arterial disease (PAD) is characterized by myofiber degeneration and loss of function in muscles of the lower limbs. Human enterovirus (HEV) infection has been implicated in the pathogenesis of a number of muscle diseases. However, its association with PAD has not been studied. In this study, we tested the hypothesis that infectious HEV is present in skeletal muscle of patients with PAD and is associated with severity of disease.


RESULTS
Gastrocnemius biopsies from 37 patients with PAD and 14 controls were examined for the presence of HEV RNA, viral capsid protein, viral RNA copy number, and viral infectivity. HEV RNA was detected in 54% of the biopsies from patients with PAD but was not detected in muscle biopsies from control patients. This difference in prevalence among PAD and control patients was significant at P<0.001. Viral RNA copy numbers were increased significantly at the later stages of disease; Fontaine Stage IV (10(5.50) copies/mg muscle wet weight, at P<0.005) and Stage III (10(4.87) copies/mg, at P<0.010) compared to Stage II (10(2.50) copies/mg). Viral replication was confirmed by the presence of the negative-strand of viral RNA in all specimens positive for HEV RNA. Cultures of HeLa and human skeletal muscle cells treated with muscle homogenates showed HEV replication and the presence of HEV capsid protein.


CONCLUSIONS
Our data identified infectious HEV in the gastrocnemius of PAD patients but not in controls. Viral copy number and prevalence of infection were higher in the later stages of disease. Our data point to the need for further studies to determine the contribution of HEV infection to the pathophysiology of PAD.
Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE.
Julian K S
JK
Kim
Zhen
Z
Zhu
George
G
Casale
Panagiotis
P
Koutakis
Rodney D
RD
McComb
Stanley
S
Swanson
Jonathan
J
Thompson
Dimitrios
D
Miserlis
Jason M
JM
Johanning
Gleb
G
Haynatzki
Iraklis I
II
Pipinos
D000368:Aged; D001706:Biopsy; D036022:Capsid Proteins / Q000302:isolation & purification; D016022:Case-Control Studies; D004770:Enterovirus / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007484:Iowa / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000821:virology*; D009329:Nebraska / Q000453:epidemiology; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D015995:Prevalence; D012367:RNA, Viral / Q000302:isolation & purification; D012307:Risk Factors; D012720:Severity of Illness Index; D019562:Viral Load; D014779:Virus Replication
D036022:Capsid Proteins; D012367:RNA, Viral
coxsackievirus; human enterovirus; peripheral arterial disease; skeletal muscle degeneration