tetano
Editor, Senior Moderator
J Virol. 2014 Sep 3. pii: JVI.02341-14. [Epub ahead of print]
Severity of clinical disease and pathology in ferrets experimentally infected with influenza viruses is influenced by inoculum volume.
Moore IN1, Lamirande EW1, Paskel M1, Donahue D2, Qin J3, Subbarao K4.
Author information
Abstract
Ferrets are a valuable model for influenza pathogenesis, virus transmission and antiviral therapy studies. However, the contributions of volume of inoculum administered and the ferret's respiratory tract anatomy to disease outcome have not been explored. We noted variation in clinical disease outcomes and the volume of inoculum administered and investigated these differences by administering two influenza viruses (A/California/07/2009 (H1N1pdm) and A/Minnesota/11/2010 (H3N2v) to ferrets intranasally at a dose of 106 TCID50 in a range of inoculum volumes (0.2, 0.5 or 1.0ml), and followed viral replication, clinical disease and pathology over 6 days. Clinical illness and respiratory tract pathology were most severe and most consistent when the viruses were administered in a volume of 1.0 ml. Using a modified micro-CT imaging method and examining gross specimens, we found that the right main stem bronchus was consistently larger in diameter than the left main stem bronchus though the latter was longer and straighter. These anatomic features likely influence the distribution of inoculum in the lower respiratory tract. A 1.0 ml volume of inoculum is optimal for delivery of virus to the lower respiratory tract of ferrets, particularly when evaluation of clinical disease is desired. Furthermore, we highlight important anatomical features of the ferret lung that influence the kinetics of viral replication, clinical disease severity and lung pathology.
IMPORTANCE:
Ferrets are a valuable model for influenza pathogenesis, virus transmission and antiviral therapy studies. Clinical disease in ferrets is an important parameter in evaluating the virulence of novel influenza viruses and findings are extrapolated to virulence in humans. Therefore, the accuracy and reproducibility of data between laboratories is highly desirable. We have found that, even when the same virus was administered at similar doses, a range of clinical disease outcomes were reported by different investigators, from asymptomatic infection to severe weight loss, ocular and nasal discharge, sneezing and lethargy. We found that a wide range of inoculum volumes were used to experimentally infect ferrets and we sought to determine whether the variations in disease outcome were the result of the volume of inoculum administered. These data highlight some less explored features of the model, methods of experimental infection, and clinical disease outcomes in a research setting.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25187553
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25187553
Severity of clinical disease and pathology in ferrets experimentally infected with influenza viruses is influenced by inoculum volume.
Moore IN1, Lamirande EW1, Paskel M1, Donahue D2, Qin J3, Subbarao K4.
Author information
Abstract
Ferrets are a valuable model for influenza pathogenesis, virus transmission and antiviral therapy studies. However, the contributions of volume of inoculum administered and the ferret's respiratory tract anatomy to disease outcome have not been explored. We noted variation in clinical disease outcomes and the volume of inoculum administered and investigated these differences by administering two influenza viruses (A/California/07/2009 (H1N1pdm) and A/Minnesota/11/2010 (H3N2v) to ferrets intranasally at a dose of 106 TCID50 in a range of inoculum volumes (0.2, 0.5 or 1.0ml), and followed viral replication, clinical disease and pathology over 6 days. Clinical illness and respiratory tract pathology were most severe and most consistent when the viruses were administered in a volume of 1.0 ml. Using a modified micro-CT imaging method and examining gross specimens, we found that the right main stem bronchus was consistently larger in diameter than the left main stem bronchus though the latter was longer and straighter. These anatomic features likely influence the distribution of inoculum in the lower respiratory tract. A 1.0 ml volume of inoculum is optimal for delivery of virus to the lower respiratory tract of ferrets, particularly when evaluation of clinical disease is desired. Furthermore, we highlight important anatomical features of the ferret lung that influence the kinetics of viral replication, clinical disease severity and lung pathology.
IMPORTANCE:
Ferrets are a valuable model for influenza pathogenesis, virus transmission and antiviral therapy studies. Clinical disease in ferrets is an important parameter in evaluating the virulence of novel influenza viruses and findings are extrapolated to virulence in humans. Therefore, the accuracy and reproducibility of data between laboratories is highly desirable. We have found that, even when the same virus was administered at similar doses, a range of clinical disease outcomes were reported by different investigators, from asymptomatic infection to severe weight loss, ocular and nasal discharge, sneezing and lethargy. We found that a wide range of inoculum volumes were used to experimentally infect ferrets and we sought to determine whether the variations in disease outcome were the result of the volume of inoculum administered. These data highlight some less explored features of the model, methods of experimental infection, and clinical disease outcomes in a research setting.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25187553
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25187553