Effect of full-length and truncated variants of LL-37 on dengue virus infection and immunomodulatory effects of LL-37 in dengue virus infected U937-DC-SIGN cells

摘要

LL-37 is an antiviral and an immunomodulatory antimicrobial peptide present in humans. The present study investigated the inhibitory effect of LL-37 and its truncated variants on the infection of all the four serotypes of dengue virus (DENV) by immunofiuorescence assays and the immunomodulatory activity of LL-37 on the expression of genes coding for pattern recognition receptors and components involved in type I interferon (IFN) signalling in DENV-2 infected U937-DC-SIGN cells using Taqman based assays. The results revealed the requirement of full length LL-37 to inhibit the infection of all the four serotypes of DENV when the viruses were pretreated with the peptide. However, the inhibitory effect of LL-37 on DENV-4 was not significant with regard to production of infectious virus particles. Truncated variants of LL-37 including LL-13, LL-23 and LL-18-37 had no effect on the viral infection. LL-37 significantly down regulated the expression of IFIH1, OAS1 and ISG15 genes in DENV-2 infected cells compared to DENV-2 infected cells without LL-37 treatment (P< 0.0001 for OAS1 and P < 0.05 for IFIH1 and ISG15). The results suggest the prophylactic utility of the full length LL-37 against all the four serotypes of DENV. Apart from its antiviral activity, LL-37 might also play an immunoregulatory role by modulating type I IFN response.