Assessment of Prolonged Dengue Virus Infection in Dermal Fibroblasts and Hair-Follicle Dermal Papilla Cells.

Kai-Che Wei,Li-Chen Yen,Wan-Ju Wei,Yi-Shan Liu,Tsung-Hsien Chang

doi:10.3390/v12030267

Abstract

Dengue virus (DENV)-mediated hair loss is one of the post-dengue fatigue syndromes and its pathophysiology remains unknown. Whether long-term or persistent infection with DENV in the scalp results in hair loss is unclear. In this study, we cultured human dermal fibroblasts (WS1 cells) and primary human hair-follicle dermal papilla cells (HFDPCs) in the long term with DENV-2 infection. The production of virion, the expression of inflammatory and anti-virus genes, and their signaling transduction activity in the infected cells were analyzed. DENV-2 NS3 protein and DENV-2 5′ UTR RNA were detected in fibroblasts and HFDPCs that were subjected to long-term infection with DENV-2 for 33 days. A significant amount of DENV-2 virion was produced by both WS1 cells and HFDPCs in the first two days of acute infection. The virion was also detected in WS1 cells that were infected in the long term, but HFDPCs failed to produce DENV-2 after long-term culture. Type I and type III interferons, and inflammatory cytokines were highly expressed in the acute phase of DENV infection in HFPDC and WS1 cells. However, in the long-term cultured cells, modest levels of anti-viral protein genes were expressed and we observed reduced signaling activity, which was correlated with the level of virus production changes. Long-term infection of DENV-2 downregulated the expression of hair growth regulatory factors, such as Rip1, Wnt1, and Wnt4. This in vitro study shows that the long-term infection with DENV-2 in dermal fibroblasts and dermal papilla cells may be involved with the prolonged-DENV-infection-mediated hair loss of post-dengue fatigue syndrome. However, direct evidence for viral replication in the human hair of a dengue victim or animal infection model is required.

Highlights

Dengue fever is an acute infectious disease caused by the dengue virus (DENV), which is transmitted by mosquitoes to humans
The results showed that WS1 cells are susceptible to DENV-2, as expected (Figure 1A)
The DENV-2 infectivity was counted using an immunofluorescence assay, which showed that approximately 80% cells with multiplicities of infection (MOI) 5 and 10 presented NS3 (Figure 1C); the increased immunofluorescence intensity of NS3 was determined in a MOI-dependent manner (Figure 1D)

Summary

Introduction

Dengue fever is an acute infectious disease caused by the dengue virus (DENV), which is transmitted by mosquitoes to humans. About 400 million people are infected per year worldwide. More than 3 billion people are residing in areas threatened by DENV. Viruses 2020, 12, 267 infection [1]. There are four different serotypes of the virus (DENV types 1–4), and each type can cause disease. The levels of DENV infection vary from mild to severe, ranging from self-limited febrile dengue fever, skin rash, drowsiness, agitation, liver enlargement, and dengue hemorrhagic fever (DHF), to even death. A second DENV infection may result in life-threatening dengue shock syndrome (DSS). No specific therapy is available for the infection other than supportive treatments [2,3]

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Results

Conclusion