title: Salidroside exhibits anti-dengue virus activity by upregulating host innate immune factors.
abstract: Dengue is an arboviral disease with no effective therapy available. Therefore, there is an urgent need to find a potent antiviral agent against dengue virus (DENV). In the present study, salidroside, a main bioactive compound of Rhodiola rosea, was evaluated for its antiviral potential against DENV serotype-2 infection and its effect on host innate immune factors. Antiviral effects of salidroside were examined in DENV-infected cells by western blotting, flow cytometry and real-time PCR. Its underlying mechanism involved in antiviral action was determined by evaluating expression of host innate immune factors including RIG-I, IRF-3, IRF-7, PKR, P-eIF2α and NF-κB. Salidroside potently inhibited DENV infection by decreasing DENV envelope protein expression more than tenfold. Salidroside exerts its antiviral activity by increasing expression of RNA helicases such as RIG-I, thereby initiating a downstream signaling cascade that induces upregulation of IRF-3 and IRF-7. It prevents viral protein synthesis by increasing the expression of PKR and P-eIF2α while decreasing NF-κB expression. It was also found to induce the expression of IFN-α. In addition, the number of NK cells and CD8+T cells were also found to be increased by salidroside treatment in human PBMCs, which are important in limiting DENV replication during early stages of infection. The findings presented here suggest that salidroside exhibits antiviral activity against DENV by inhibiting viral protein synthesis and boosting host immunity by increasing the expression of host innate immune factors and hence could be considered for the development of an effective therapeutic agent against DENV infection.
authors: Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Lucknow Road, Timarpur, Delhi, 110054, India.
authors: Navita
authors: N
authors: Sharma
authors: Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Lucknow Road, Timarpur, Delhi, 110054, India. kpmpgi@rediffmail.com.
authors: K P
authors: KP
authors: Mishra
authors: Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Lucknow Road, Timarpur, Delhi, 110054, India.
authors: Lilly
authors: L
authors: Ganju
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003716:Dengue Virus / Q000187:drug effects* / Q000276:immunology*; D020869:Gene Expression Profiling; D005960:Glucosides / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis* / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D010636:Phenols / Q000302:isolation & purification / Q000378:metabolism*; D029771:Rhodiola / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000998:Antiviral Agents; D005960:Glucosides; D007155:Immunologic Factors; D010636:Phenols; D014764:Viral Proteins; C009172:rhodioloside