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Experimental infection of mice with avian paramyxovirus serotypes 1 to 9.

Khattar SK, Kumar S, Xiao S, Collins PL, Samal SK - PLoS ONE (2011)

Bottom Line: Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2>6, 9>7.However, disease was short-lived.Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection.

View Article: PubMed Central - PubMed

Affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
The nine serotypes of avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds worldwide. APMV-1, also called Newcastle disease virus, was shown to be attenuated in non-avian species and is being developed as a potential vector for human vaccines. In the present study, we extended this evaluation to the other eight serotypes by evaluating infection in BALB/c mice. Mice were inoculated intranasally with a prototype strain of each of the nine serotypes and monitored for clinical disease, gross pathology, histopathology, virus replication and viral antigen distribution, and seroconversion. On the basis of multiple criteria, each of the APMV serotypes except serotype 5 was found to replicate in mice. Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2>6, 9>7. However, disease was short-lived. The other serotypes produced no evident clinical disease. Replication of all of the APMVs except APMV-5 in the nasal turbinates and lungs was confirmed by the recovery of infectious virus and by substantial expression of viral antigen in the epithelial lining detected by immunohistochemistry. Trace levels of infectious APMV-4 and -9 were detected in the brain of some animals; otherwise, no virus was detected in the brain, small intestine, kidney, or spleen. Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection. All of the mice infected with the APMVs except APMV-5 produced serotype-specific HI serum antibodies, confirming a lack of replication of APMV-5. Taken together, these results demonstrate that all APMV serotypes except APMV-5 are capable of replicating in mice with minimal disease and pathology.

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Immunohistochemistry of sections of lungs (3a) and nasal turbinates (3b) harvested from mice 3 dpi with each of the 9 APMV serotypes.Mice were mock-infected (panel A) or infected with APMV-1 (panel B), APMV-2 (panel C), APMV-3 (panel D), APMV-4 (panel E), APMV-5 (panel F), APMV-6 (panel G), APMV-7 (panel H), APMV-8 (panel I), and APMV-9 (panel J). Immunofluoresence was performed with polyclonal antiserum specific to the respective serotype N protein (magnification, ×400). In sections of the lungs from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium (Fig. 3a). In sections of the nasal turbinates from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium, at the apical surface of the ciliated epithelial cells and in the cytoplasm (Fig. 3b). Bronchioles are shown by arrow.
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pone-0016776-g003: Immunohistochemistry of sections of lungs (3a) and nasal turbinates (3b) harvested from mice 3 dpi with each of the 9 APMV serotypes.Mice were mock-infected (panel A) or infected with APMV-1 (panel B), APMV-2 (panel C), APMV-3 (panel D), APMV-4 (panel E), APMV-5 (panel F), APMV-6 (panel G), APMV-7 (panel H), APMV-8 (panel I), and APMV-9 (panel J). Immunofluoresence was performed with polyclonal antiserum specific to the respective serotype N protein (magnification, ×400). In sections of the lungs from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium (Fig. 3a). In sections of the nasal turbinates from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium, at the apical surface of the ciliated epithelial cells and in the cytoplasm (Fig. 3b). Bronchioles are shown by arrow.

Mentions: The remaining half of each of the tissue samples isolated on 3 dpi and 14 dpi from the mice infected with the APMV serotypes was fixed and embedded in paraffin, and tissue sections were prepared. The tissue sections representing all of the collected tissue samples from the virus-infected and mock-infected animals from 3 dpi and 14 dpi were deparaffinized and immunostained using polyclonal antiserum specific to the N protein of the corresponding APMV serotype. Large amounts of APMV-specific N antigen was detected at 3 dpi by immunofluorescence staining of lungs and nasal turbinate tissue samples of mice infected with all the serotypes of APMV except serotype 5, which was negative (Fig. 3a and 3b). In the lungs of mice infected with each of the APMV serotypes except serotype 5, the viral antigen was localized mainly on the respiratory epithelium lining small and medium bronchi. In nasal turbinates of mice infected with each of the APMV serotypes except serotype 5, the virus specific immunoflourescence was observed on nasal epithelium lining the turbinate bone. No viral N antigen was detected in tissue samples from brain, spleen, kidney and small intestine of mice 3 dpi or 14 dpi with any the APMV serotypes, or from the lungs and nasal turbinates 14 dpi.


Experimental infection of mice with avian paramyxovirus serotypes 1 to 9.

Khattar SK, Kumar S, Xiao S, Collins PL, Samal SK - PLoS ONE (2011)

Immunohistochemistry of sections of lungs (3a) and nasal turbinates (3b) harvested from mice 3 dpi with each of the 9 APMV serotypes.Mice were mock-infected (panel A) or infected with APMV-1 (panel B), APMV-2 (panel C), APMV-3 (panel D), APMV-4 (panel E), APMV-5 (panel F), APMV-6 (panel G), APMV-7 (panel H), APMV-8 (panel I), and APMV-9 (panel J). Immunofluoresence was performed with polyclonal antiserum specific to the respective serotype N protein (magnification, ×400). In sections of the lungs from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium (Fig. 3a). In sections of the nasal turbinates from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium, at the apical surface of the ciliated epithelial cells and in the cytoplasm (Fig. 3b). Bronchioles are shown by arrow.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3037383&req=5

pone-0016776-g003: Immunohistochemistry of sections of lungs (3a) and nasal turbinates (3b) harvested from mice 3 dpi with each of the 9 APMV serotypes.Mice were mock-infected (panel A) or infected with APMV-1 (panel B), APMV-2 (panel C), APMV-3 (panel D), APMV-4 (panel E), APMV-5 (panel F), APMV-6 (panel G), APMV-7 (panel H), APMV-8 (panel I), and APMV-9 (panel J). Immunofluoresence was performed with polyclonal antiserum specific to the respective serotype N protein (magnification, ×400). In sections of the lungs from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium (Fig. 3a). In sections of the nasal turbinates from mice infected with different APMVs, immunofluorescence was evident around the bronchial epithelium, at the apical surface of the ciliated epithelial cells and in the cytoplasm (Fig. 3b). Bronchioles are shown by arrow.
Mentions: The remaining half of each of the tissue samples isolated on 3 dpi and 14 dpi from the mice infected with the APMV serotypes was fixed and embedded in paraffin, and tissue sections were prepared. The tissue sections representing all of the collected tissue samples from the virus-infected and mock-infected animals from 3 dpi and 14 dpi were deparaffinized and immunostained using polyclonal antiserum specific to the N protein of the corresponding APMV serotype. Large amounts of APMV-specific N antigen was detected at 3 dpi by immunofluorescence staining of lungs and nasal turbinate tissue samples of mice infected with all the serotypes of APMV except serotype 5, which was negative (Fig. 3a and 3b). In the lungs of mice infected with each of the APMV serotypes except serotype 5, the viral antigen was localized mainly on the respiratory epithelium lining small and medium bronchi. In nasal turbinates of mice infected with each of the APMV serotypes except serotype 5, the virus specific immunoflourescence was observed on nasal epithelium lining the turbinate bone. No viral N antigen was detected in tissue samples from brain, spleen, kidney and small intestine of mice 3 dpi or 14 dpi with any the APMV serotypes, or from the lungs and nasal turbinates 14 dpi.

Bottom Line: Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2>6, 9>7.However, disease was short-lived.Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection.

View Article: PubMed Central - PubMed

Affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
The nine serotypes of avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds worldwide. APMV-1, also called Newcastle disease virus, was shown to be attenuated in non-avian species and is being developed as a potential vector for human vaccines. In the present study, we extended this evaluation to the other eight serotypes by evaluating infection in BALB/c mice. Mice were inoculated intranasally with a prototype strain of each of the nine serotypes and monitored for clinical disease, gross pathology, histopathology, virus replication and viral antigen distribution, and seroconversion. On the basis of multiple criteria, each of the APMV serotypes except serotype 5 was found to replicate in mice. Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2>6, 9>7. However, disease was short-lived. The other serotypes produced no evident clinical disease. Replication of all of the APMVs except APMV-5 in the nasal turbinates and lungs was confirmed by the recovery of infectious virus and by substantial expression of viral antigen in the epithelial lining detected by immunohistochemistry. Trace levels of infectious APMV-4 and -9 were detected in the brain of some animals; otherwise, no virus was detected in the brain, small intestine, kidney, or spleen. Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection. All of the mice infected with the APMVs except APMV-5 produced serotype-specific HI serum antibodies, confirming a lack of replication of APMV-5. Taken together, these results demonstrate that all APMV serotypes except APMV-5 are capable of replicating in mice with minimal disease and pathology.

Show MeSH
Related in: MedlinePlus