ZIKA Virus Infection And Host Response

Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which can cause microcephaly, a birth defect where a baby's head is smaller than usual. Additionally, it is associated with Guillain-Barré syndrome, a neurological disorder that could lead to paralysis and even death. Zika virus illness has been described as self-limited and moderate in severity with the common findings of malaise, headache, fever, joint aches, a maculopapular rash, and inflammation of the conjunctiva. However, an alarming number of birth defects, including microcephaly, have been attributed to Zika virus infection occurring in the first two trimesters of pregnancy (Ref.1). 

 

Zika virus is an enveloped, icosahedral positive single-stranded RNA virus and has a genome of 10 kb, which encodes three structural proteins (capsid, premembrane/ membrane, and envelope) and seven nonstructural proteins. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, are all permissive to ZIKV infection. Several entry and/or adhesion factors, among which DC-SIGN, AXL, TYRO3, and to a lesser extent, TIM-1, permitted ZIKV entry with a major role for the TAM receptor AXL. Infection of dermal fibroblasts with ZIKV upregulates the expression of pathogen recognition receptor (PRR)s, including toll-like receptor (TLR)3, RIG-I and MDA-5, which subsequently trigger the expression of type I IFNs, IFN stimulated genes, including OAS2, ISG15 and MX1, and inflammatory chemokines. ZIKV is sensitive to the antiviral effects of both type I and type II interferons. ZIKV infection also upregulates the autophagic pathway in infected skin fibroblasts. Moreover, the autophagic marker LC3 colocalizes with viral proteins within ZIKV-infected cells, and the infection can be reduced by treatment with the autophagy inhibitor 3-methyladenine, whereas upregulation of autophagy using Torin 1 increases ZIKV replication. Skin dendritic cells in particular look to be an important Zika target since they have also been proposed to facilitate the spread of dengue virus. Assessment of other vulnerable cell types awaits further investigation (Ref.2 and 3).