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.
Bravo
Fernando J
FJ
Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 6014, Cincinnati, OH 45229-3039, USA.
Cardin
Rhonda D
RD
Bernstein
David I
DI
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