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Hepatitis C virus core protein enhances HIV‐1 replication in human macrophages through TLR2, JNK, and MEK1/2‐dependent upregulation of TNF‐α and IL‐6
Author(s) -
Swaminathan Gokul,
Pascual Daniel,
Rival Germaine,
Perales-Linares Renzo,
Martin-Garcia Julio,
Navas-Martin Sonia
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.08.009
Subject(s) - tlr2 , downregulation and upregulation , virology , hepatitis c virus , tumor necrosis factor alpha , viral replication , biology , macrophage , virus , immunology , inflammation , in vitro , gene , tlr4 , biochemistry
Despite their differential cell tropisms, HIV‐1 and HCV dramatically influence disease progression in coinfected patients. Macrophages are important target cells of HIV‐1. We hypothesized that secreted HCV core protein might modulate HIV‐1 replication. We demonstrate that HCV core significantly enhances HIV‐1 replication in human macrophages by upregulating TNF‐α and IL‐6 via TLR2‐, JNK‐, and MEK1/2‐dependent pathways. Furthermore, we show that TNF‐α and IL‐6 secreted from HCV core‐treated macrophages reactivates monocytic U1 cells latently infected with HIV‐1. Our studies reveal a previously unrecognized role of HCV core by enhancing HIV‐1 infection in macrophages.