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Dengue virus antibodies enhance Zika virus infection
Title
Dengue virus antibodies enhance Zika virus infection.
Creator
Paul, Lauren M, Carlin, Eric R, Jenkins, Meagan M, Tan, Amanda L, Barcellona, Carolyn M, Nicholson, Cindo O, Michael, Scott F, Isern, Sharon
Abstract/Description
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted...
Show moreFor decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.
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Date Issued
2016-12-16
Identifier
10.1038/cti.2016.72, fgcu_ir_000083, http://doi.wiley.com/10.1038/cti.2016.72
Format
Citation
Release of Dengue Virus Genome Induced by a Peptide Inhibitor
Title
Release of Dengue Virus Genome Induced by a Peptide Inhibitor.
Creator
Lok, Shee-Mei, Costin, Joshua M., Hrobowski, Yancey M., Hoffmann, Andrew R., Rowe, Dawne K., Kukkaro, Petra, Holdaway, Heather, Chipman, Paul, Fontaine, Krystal A., Holbrook,...
Show moreLok, Shee-Mei, Costin, Joshua M., Hrobowski, Yancey M., Hoffmann, Andrew R., Rowe, Dawne K., Kukkaro, Petra, Holdaway, Heather, Chipman, Paul, Fontaine, Krystal A., Holbrook, Michael R., Garry, Robert F., Kostyuchenko, Victor, Wimley, William C., Isern, Sharon, Rossmann, Michael G., Michael, Scott F., Lee, Young-Min
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Abstract/Description
Dengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. The mimetic peptide, DN59, consists of residues corresponding to the membrane interacting, amphipathic stem region of the dengue virus envelope (E) glycoprotein. This peptide is inhibitory to all four serotypes of dengue virus, as well as other flaviviruses. Cryo-electron microscopy image reconstruction of dengue virus particles incubated with DN59 showed that the virus particles...
Show moreDengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. The mimetic peptide, DN59, consists of residues corresponding to the membrane interacting, amphipathic stem region of the dengue virus envelope (E) glycoprotein. This peptide is inhibitory to all four serotypes of dengue virus, as well as other flaviviruses. Cryo-electron microscopy image reconstruction of dengue virus particles incubated with DN59 showed that the virus particles were largely empty, concurrent with the formation of holes at the five-fold vertices. The release of RNA from the viral particle following incubation with DN59 was confirmed by increased sensitivity of the RNA genome to exogenous RNase and separation of the genome from the E protein in a tartrate density gradient. DN59 interacted strongly with synthetic lipid vesicles and caused membrane disruptions, but was found to be non-toxic to mammalian and insect cells. Thus DN59 inhibits flavivirus infectivity by interacting directly with virus particles resulting in release of the genomic RNA.
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Date Issued
2012-11-30
Identifier
10.1371/journal.pone.0050995, fgcu_r_000058, http://dx.plos.org/10.1371/journal.pone.0050995
Format
Citation