These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Unfolded protein response (UPR) gene expression during antibody-dependent enhanced infection of cultured monocytes correlates with dengue disease severity.
    Author: Paradkar PN, Ooi EE, Hanson BJ, Gubler DJ, Vasudevan SG.
    Journal: Biosci Rep; 2011 Jun; 31(3):221-30. PubMed ID: 20858223.
    Abstract:
    DENV (dengue virus) induces UPR (unfolded protein response) in the host cell, which strikes a balance between pro-survival and pro-apoptotic signals. We previously showed that Salubrinal, a drug that targets the UPR, inhibits DENV replication. Here, we examine the impact on UPR after direct or ADE (antibody-dependent enhanced) infection of cells with DENV clinical isolates. THP-1 cells in the presence of subneutralizing concentration of humanized antibody 4G2 (cross-reactive with flavivirus envelope protein) or HEK-293 cells (human embryonic kidney 293 cells) were infected with DENV-1-4 serotypes. UPR gene expression was monitored under these infection conditions using real-time RT-PCR (reverse transcription-PCR) and Western blots to analyse serotype-dependent variations. Subsequently, in a blinded study, strain-specific differences were compared between DENV-2 clinical isolates obtained from a single epidemic. Results showed that THP-1 cells were infected efficiently and equally by DENV-1-4 in the ADE mode. At 48 hpi (h post infection), DENV-1 and -3 showed a higher replication rate and induced higher expression of several UPR genes such as BiP (immunoglobulin heavy-chain-binding protein), GADD34 (growth arrest DNA damage-inducible protein 34) and CHOP [C/EBP (CCAAT/enhancer-binding protein)-homologous protein]. The ADE infection of THP-1 cells with epidemic DENV-2 high-UPR-gene-expressing strains appears to correlate with severe disease; however, no such correlation could be made when the same viruses were used to infect HEK-293 cells. Our finding that UPR gene expression in THP-1 cells during ADE infection correlates with dengue disease severity is consistent with a previous study [Morens, Marchette, Chu and Halstead (1991) Am. J. Trop. Med. Hyg. 45, 644-651] that showed that the growth of DENV 2 isolates in human peripheral blood leucocytes correlated with severe and mild dengue diseases.
    [Abstract] [Full Text] [Related] [New Search]