Dengue Viruses Are Enhanced by Distinct Populations of Serotype Cross-Reactive Antibodies in Human Immune Sera
The mosquito-borne dengue viruses (DENV) are responsible for approximately 390 million new infections worldwide each year, and an estimated 100 million of these infections lead to clinical disease. The presence of four different serotypes of DENV allows the same individual to experience more than one DENV infection. Secondary DENV infections with a different serotype are more likely to cause severe dengue disease than primary infections. One of the explanations for the greater risk of severe disease during secondary DENV infections is the phenomenon called antibody-dependent enhancement (ADE), where pre-existing DENV-specific antibodies enable entry of DENV into target host cells, and thereby enhance infection and disease. At the moment, the epitopes targeted by enhancing antibodies following a DENV infection are unclear. In the present study, we use novel techniques to fractionate human serum antibodies and test their ability to enhance DENV infection both in vitro (K562 cells) and in vivo (in a mouse model of lethal antibody-enhanced dengue disease). We found that antibodies binding both the envelope and prM proteins on the DENV virion play an important role in ADE of DENV by human immune sera. Our findings about DENV-enhancing antibodies in human immune sera are relevant to developing safe vaccines.
Vyšlo v časopise:
Dengue Viruses Are Enhanced by Distinct Populations of Serotype Cross-Reactive Antibodies in Human Immune Sera. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004386
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004386
Souhrn
The mosquito-borne dengue viruses (DENV) are responsible for approximately 390 million new infections worldwide each year, and an estimated 100 million of these infections lead to clinical disease. The presence of four different serotypes of DENV allows the same individual to experience more than one DENV infection. Secondary DENV infections with a different serotype are more likely to cause severe dengue disease than primary infections. One of the explanations for the greater risk of severe disease during secondary DENV infections is the phenomenon called antibody-dependent enhancement (ADE), where pre-existing DENV-specific antibodies enable entry of DENV into target host cells, and thereby enhance infection and disease. At the moment, the epitopes targeted by enhancing antibodies following a DENV infection are unclear. In the present study, we use novel techniques to fractionate human serum antibodies and test their ability to enhance DENV infection both in vitro (K562 cells) and in vivo (in a mouse model of lethal antibody-enhanced dengue disease). We found that antibodies binding both the envelope and prM proteins on the DENV virion play an important role in ADE of DENV by human immune sera. Our findings about DENV-enhancing antibodies in human immune sera are relevant to developing safe vaccines.
Zdroje
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Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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