Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene.
Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory tract infection for which no vaccine or antiviral treatment is available. The RSV NS1 protein seems to antagonize the host interferon (IFN) response; however, its mechanism is unknown. Here, we used a plasmid-borne small interfering RNA targeting the NS1 gene (siNS1) to examine the role of NS1 in modulating RSV infection. RSV replication was reduced in A549 cells, but not IFN-deficient Vero cells, transfected with siNS1. siNS1 induced upregulated expression of IFN-beta and IFN-inducible genes in A549 cells. siNS1-transfected human dendritic cells, upon RSV infection, produced elevated type-1 IFN and induced differentiation of naive CD4+ T cells to T helper type 1 (TH1) cells. Mice treated intranasally with siNS1 nanoparticles before or after infection with RSV showed substantially decreased virus titers in the lung and decreased inflammation and airway reactivity compared to controls. Thus, siNS1 nanoparticles may provide an effective inhibition of RSV infection in humans.
Zhang
Weidong
W
Division of Allergy and Immunology-Joy McCann Culverhouse Airway Disease Research Center, Department of Internal Medicine, University of South Florida, MDC-19-Rm 2536, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, USA.
Yang
Hong
H
Kong
Xiaoyuan
X
Mohapatra
Subhra
S
San Juan-Vergara
Homero
H
Hellermann
Gary
G
Behera
Sumita
S
Singam
Rajeswari
R
Lockey
Richard F
RF
Mohapatra
Shyam S
SS
D000998:Antiviral Agents / Q000494:pharmacology*; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D049329:Nanostructures; D034741:RNA, Small Interfering / Q000494:pharmacology*; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000235:genetics; D018417:Th1 Cells / Q000378:metabolism; D015854:Up-Regulation; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism
D000998:Antiviral Agents; D007370:Interferon Type I; D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins