Functional diversity in vascular endothelial cells: role in coxsackievirus tropism.
Six plaque-purified virus isolates were obtained from liver and heart tissues of a DBA/2 mouse infected 7 days earlier with 10(4) PFU of coxsackievirus group B type 3. Each virus isolate was assayed in vitro for infectivity to vascular endothelial cells (VEC) of the liver, lungs, and heart. Both the percentage of VEC infected and the mean progeny PFU produced per infected VEC were determined. Virus isolates from the heart showed greater infectivity and replication in heart VEC than in VEC derived from either the liver or lungs. Similarly, virus isolated from the liver preferentially infected liver VEC. Virus receptor expression varied between VEC populations, as demonstrated by binding studies with a [35S]methionine-radiolabeled heart virus and by enzyme-linked immunoadsorption assay studies with a monoclonal antibody to the coxsackievirus group B type 3 receptor on heart tissue. Finally, the heart and liver virus isolates were injected (10(4) PFU) intraperitoneally into BALB/c mice. After 7 days, the animals were sacrificed, and the hearts, livers, and lungs were evaluated for tissue injury and virus concentrations. Viruses originally isolated from the heart preferentially infected the heart when reinjected into animals and caused severe myocarditis. Viruses originally derived from the liver most consistently reinfected the liver, although significant virus concentrations were also detected in the heart. The liver virus isolates, however, were incapable of causing myocarditis. Thus, selective tropism of viruses for particular organs in vivo corresponds to the ability of these isolates to infect VEC in vitro.
Huber
S A
SA
Department of Pathology, University of Vermont, Burlington 05405-0068.
Haisch
C
C
Lodge
P A
PA
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000302:isolation & purification; D003384:Coxsackievirus Infections / Q000382:microbiology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000382:microbiology* / Q000473:pathology; D029822:Enterovirus B, Human / Q000302:isolation & purification*; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells; D006321:Heart / Q000382:microbiology; D006801:Humans; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009206:Myocardium / Q000473:pathology; D010948:Viral Plaque Assay
D000956:Antigens, Viral