Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery

Weidong Zhang; Rajeswari Singam; Gary Hellermann; Xiaoyuan Kong; Homero San Juan; Richard F. Lockey; Shuen Ju Wu; Kevin Porter; Shyam S. Mohapatra

doi:10.1186/1479-0556-2-8

Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery

Weidong Zhang, Rajeswari Singam, Gary Hellermann, Xiaoyuan Kong, Homero San Juan, Richard F. Lockey, Shuen Ju Wu, Kevin Porter, Shyam S. Mohapatra^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

Background: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). Methods: A cassette encoding siRNA targeted to a 3′ untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. Results: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. Conclusion: These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.

Original language	English
Journal	Genetic Vaccines and Therapy
Volume	2
DOIs	https://doi.org/10.1186/1479-0556-2-8
State	Published - 9 Aug 2004
Externally published	Yes

Keywords

Adeno-associated virus
Dengue virus
Gene expression
siRNA

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10.1186/1479-0556-2-8

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@article{253128bcd1c9462587ea158c1a75d97c,

title = "Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery",

abstract = "Background: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). Methods: A cassette encoding siRNA targeted to a 3′ untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. Results: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. Conclusion: These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.",

keywords = "Adeno-associated virus, Dengue virus, Gene expression, siRNA",

author = "Weidong Zhang and Rajeswari Singam and Gary Hellermann and Xiaoyuan Kong and {San Juan}, Homero and Lockey, {Richard F.} and Wu, {Shuen Ju} and Kevin Porter and Mohapatra, {Shyam S.}",

year = "2004",

month = aug,

day = "9",

doi = "10.1186/1479-0556-2-8",

language = "English",

volume = "2",

journal = "Genetic Vaccines and Therapy",

issn = "1479-0556",

}

TY - JOUR

T1 - Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery

AU - Zhang, Weidong

AU - Singam, Rajeswari

AU - Hellermann, Gary

AU - Kong, Xiaoyuan

AU - San Juan, Homero

AU - Lockey, Richard F.

AU - Wu, Shuen Ju

AU - Porter, Kevin

AU - Mohapatra, Shyam S.

PY - 2004/8/9

Y1 - 2004/8/9

N2 - Background: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). Methods: A cassette encoding siRNA targeted to a 3′ untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. Results: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. Conclusion: These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.

AB - Background: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). Methods: A cassette encoding siRNA targeted to a 3′ untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. Results: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. Conclusion: These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans.

KW - Adeno-associated virus

KW - Dengue virus

KW - Gene expression

KW - siRNA

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U2 - 10.1186/1479-0556-2-8

DO - 10.1186/1479-0556-2-8

M3 - Article

AN - SCOPUS:13444272367

SN - 1479-0556

VL - 2

JO - Genetic Vaccines and Therapy

JF - Genetic Vaccines and Therapy

ER -

Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery

Abstract

Keywords

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