Antiviral activity of the chemokine CXCL10 against West Nile virus.

Abstract

Background: West Nile virus (WNV) is an emerging arbovirus for which there is no vaccine nor antiviral treatment. Skin cells are the primary site of WNV replication following transmission by the mosquito vector. In a previous work, strong induction of CXCL10 mRNA expression was observed during in vitro infection of human primary keratinocytes with WNV. Known to be chemoattractant, CXCL10 has also been reported to exhibit antimicrobial peptide properties through direct inhibitory activity against Gram-positive and Gram-negative bacteria. The objective of this work was to investigate the antiviral properties of CXCL10 against WNV.

Methodology/principal findings: A 24-hour time-course infection of keratinocytes in the presence of CXCL10 showed a significant reduction of viral load and infectious titer in the cell culture supernatant. This inhibition of virus replication was observed when the chemokine was added to the cells before or simultaneously with the virus, suggesting pre-fusion action. In contrast, no antiviral effect was observed when CXCL10 was added 3 hours post-infection. However, incubation of the virus with CXCL10 did not show any reduction in the infectious titer, ruling out direct damage to the viral particle. In addition, expression of markers of the cells' innate immune response was not modified by adding CXCL10 during the infection. Finally, a reduction in virus attachment to the cells was demonstrated in the presence of CXCL10.

Conclusion: Our results showed antiviral activity of CXCL10 against WNV during human keratinocyte infection. Even if additional experiments are required to precisely determine its mechanism of action, CXCL10 could interfere with WNV attachment to the keratinocyte surface.