Open AccessDengue virus replication enhances labile zinc pools by modulation of ZIP8
Author(s) -
Panwar Aleksha,
Wangchuk Jigme,
Kar Meenakshi,
Lodha Rakesh,
Medigeshi Guruprasad R.
Publication year - 2021
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.13395
Subject(s) - dengue virus , dengue fever , zinc , biology , viral replication , virology , intracellular , virus , viremia , homeostasis , microbiology and biotechnology , chemistry , organic chemistry
Zinc‐dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life‐cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolished in cells infected with UV‐inactivated virus or with a DENV replication inhibitor implicating a role for zinc homeostasis in viral RNA replication. This change in free zinc was mediated by zinc transporter, ZIP8, as siRNA‐mediated knockdown of ZIP8 resulted in abrogation of increase in free zinc levels leading to significant reduction in DENV titers suggesting a crucial role for ZIP8 in early stages of DENV replication. Furthermore, elevated free zinc levels correlated with high copy numbers of dengue genome in peripheral blood leukocytes obtained from dengue patients compared to healthy controls suggesting a critical role for zinc homeostasis in dengue infection. Take Aways Dengue virus utilises cellular zinc homeostasis during replication of its RNA. ZIP8 upregulates free zinc levels during dengue virus replication. Enhanced viremia associates with elevated intracellular free zinc in dengue.