Infection of Zika virus needs help of host receptors. Zika virus causes a mosquito-borne disease transmitted by the Aedes genus. Human skin plays an important role in the entry of Zika virus and in the induction of antiviral immune responses.
Several entry receptor and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1 or TIM-4, permitted ZIKV entry, with a major role for the TAM receptor AXL. AXL is a key receptor being responsible for Zika virus entry. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing.
An article written by Rodolphe Hamel said, the expression of either DC-SIGN or AXL strongly enhanced viral infection already at an MOI of 0.1, resulting in about 50% ZIKV-infected cells. Tyro3-expressing HEK293T cells were also highly permissive for ZIKV, with nearly 70% of the cells infected with the virus. In contrast, the expression of TIM-1 or TIM-4 had only modest or marginal effects on ZIKV entry.
After using combination of anti-TIM-1 and anti-AXL antibodies can completely abrogated Zika virus infection. The result of RNA silencing technique was same as the neutralizing antibodies. ZIKV infection was only slightly reduced in TIM-1-silenced cells, strongly inhibited in AXL silenced cells, and totally abrogated when both genes were silenced.
After doing another experiment to explain the importance of AXL, they get result as this. The presence of specific AXL siRNA totally inhibited AXL expression and effectively abrogated the infection with either virus, thus demonstrating the importance of AXL in the permissiveness of human skin fibroblasts to infection and replication of ZIKV.
In the article, they use human qPCR array covering 84 human antiviral genes to test the antiviral gene expression following Zika virus infection.
TLR3, DDX58/RIG-I, MDA5/IFIH1 mRNA expression are enhanced by Zika virus infection. The detection of viral PAMPs by TLR3 and other PRRs initiates downstream signaling pathways that account for the enhancement of transcription factors known to mobilize the antiviral machinery.
IRF7 as a transcription factor locating on the promoters of type I IFN genes is also increased in Zika virus infected cells. So, IFNa and IFNb gene expression as well as OAS2, ISG15, MX1 are also increased.
CXCL10 as well as the inflammatory antiviral chemokine CCL5 are also induced by Zika virus
ZIKV infection of skin fibroblasts was also found to activate certain inflammasome components, as evidenced by a strong increase in the expression of AIM2 and interleukin-1β (IL-1β) transcripts.
Inhibition of TLR3 expression can increase viral RNA copy. So, TLR3 plays an important role in the induction of an antiviral response against Zika virus.
If the primary skin fibroblasts were pretreated with increasing doses of recombinant human IFN-α, IFN-β, or IFN-γ, viral replication can be strongly inhibited. ZIKV is highly sensitive to the antiviral effects of both type I and type II IFNs.
Zika virus and cytokines
Zika virus and host receptors
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