Mouse model of respiratory syncytial virus infection to evaluate antiviral activity in vivo.
In this study, we have developed a practical mouse model for evaluating in vivo the antiviral activity of compounds against respiratory syncytial virus (RSV) infection. BALB/c mice are not particularly susceptible to RSV infection; however, infection rates were improved by pretreatment with the immunosuppressive agent cyclophosphamide (CYP). When mice were inoculated intranasally with RSV A2 strain, the pulmonary RSV titres of CYP-pretreated 10-week-old mice were higher than those of untreated 10-week-old and 28-week-old mice, peaking on days 4 and 5 post-infection. Sections of lung from RSV-infected mice pretreated with CYP, taken on day 4 post-inoculation, showed widespread evidence of interstitial pneumonia and other significant pathological changes. We also confirmed that ribavirin, a representative antiviral agent, significantly reduced the pulmonary RSV titres of mice pretreated with CYP when administered intraperitoneally.
Sudo
K
K
Rational Drug Design Laboratories, Fukushima, Japan. sudou.kenji@yamanouchi.co.jp
Watanabe
W
W
Mori
S
S
Konno
K
K
Shigeta
S
S
Yokota
T
T
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006367:HeLa Cells; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D017563:Lung Diseases, Interstitial / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D012254:Ribavirin / Q000627:therapeutic use
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D012254:Ribavirin; D003520:Cyclophosphamide