A model of human cytomegalovirus infection in severe combined immunodeficient mice.
Animal models for the evaluation of therapies against human cytomegalovirus (HCMV) are limited due to the species-specific replication of CMV. Models utilizing human fetal tissues implanted into SCID mice have been used but tend to be labor intensive and require human tissues. We therefore developed a model using HCMV-infected human foreskin fibroblasts (HFF) seeded onto a biodegradable gelatin matrix (Gelfoam). Infected HFFs are then implanted subcutaneously into SCID mice. We next evaluated two antivirals in this model. Treatment from days 0 to 5 with ganciclovir (GCV) produced a marginally significant reduction in viral titer while treatment from days 0 to 14 resulted in a more significant reduction in viral titers of 1.47 log(10)pfu/ml (P<0.0001). Viral titers were similarly reduced in a group receiving GCV treatment from days 7 to 14 post-implantation (1.50 log(10)pfu/ml, P<0.0001). Cidofovir therapy from days 7 to 14 reduced viral titers by almost 2 log(10)pfu/ml (from 3.51+/-0.31 log(10)pfu/ml in untreated animals to 1.56+/-0.40 log(10)pfu/ml in treated animals, P<0.0001). These results indicate that the Gelfoam-HCMV SCID mouse model is suitable for the in vivo evaluation of new antivirals against HCMV and is simpler and more convenient than previous models.
Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 6014, Cincinnati, OH 45229-3039, USA.
Fernando J
FJ
Bravo
Rhonda D
RD
Cardin
David I
DI
Bernstein
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D018929:Cell Culture Techniques; D002460:Cell Line; D000077404:Cidofovir; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D015774:Ganciclovir / Q000627:therapeutic use; D005781:Gelatin Sponge, Absorbable; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D063065:Organophosphonates / Q000627:therapeutic use; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir