Intranasal IFN-gamma gene transfer protects BALB/c mice against respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) is a major respiratory pathogen in infants, young children and the elderly and causes severe bronchiolitis and asthma. In an effort to develop a preventive IFN-gamma therapy against RSV infection, an intranasal gene transfer strategy was utilized. Intranasal administration of a plasmid expressing the IFN-gamma cDNA (pIFN-gamma) resulted in the expression of IFN-gamma in murine lungs and decreased RSV replication. The mice administered with pIFN-gamma and then infected with RSV exhibited a significant decrease in broncho-alveolar lavage lymphocyte and neutrophil counts. A significant reduction in epithelial cell damage, infiltration of mononuclear cells in the peribronchiolar and perivascular regions, and thickening of the septa was observed in the lungs of mice treated with pIFN-gamma when compared to controls. These results suggest that intranasal IFN-gamma gene transfer results in decreased RSV replication and pulmonary inflammation and may be useful against RSV infection.
Kumar
M
M
The Joy McCann Culverhouse Airway Disease Research Center, Division of Allergy and Immunology, The University of South Florida College of Medicine and VA Hospital, Tampa, FL 33612, USA.
Behera
A K
AK
Matsuse
H
H
Lockey
R F
RF
Mohapatra
S S
SS
D000281:Administration, Intranasal; D000818:Animals; D005260:Female; D018014:Gene Transfer Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D015848:Interleukin-5 / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D014779:Virus Replication
D015848:Interleukin-5; D012333:RNA, Messenger; D007371:Interferon-gamma