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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Virol
2016 ; 90
(7
): 3428-38
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ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus
Growth through Protein ISGylation
#MMPMID26763998
González-Sanz R
; Mata M
; Bermejo-Martín J
; Álvarez A
; Cortijo J
; Melero JA
; Martínez I
J Virol
2016[Jan]; 90
(7
): 3428-38
PMID26763998
show ga
Human respiratory syncytial virus (RSV), for which neither a vaccine nor an
effective therapeutic treatment is currently available, is the leading cause of
severe lower respiratory tract infections in children. Interferon-stimulated gene
15 (ISG15) is a ubiquitin-like protein that is highly increased during viral
infections and has been reported to have an antiviral or a proviral activity,
depending on the virus. Previous studies from our laboratory demonstrated strong
ISG15 upregulation during RSV infection in vitro. In this study, an in-depth
analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression
and small interfering RNA (siRNA)-silencing experiments, along with ISG15
knockout (ISG15(-/-)) cells, revealed an anti-RSV effect of the molecule.
Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral
activity via protein ISGylation. This antiviral activity requires high levels of
ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also
upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal
washes from infants infected with RSV, pointing to a possible antiviral role of
the molecule in vivo. These results advance our understanding of the innate
immune response elicited by RSV and open new possibilities to control infections
by the virus. IMPORTANCE: At present, no vaccine or effective treatment for human
respiratory syncytial virus (RSV) is available. This study shows that
interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein
ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load
in nasopharyngeal washes from children, indicating that ISG15 may also have an
antiviral role in vivo. These results improve our understanding of the innate
immune response to RSV and identify ISG15 as a potential target for virus
control.