16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Recognition of heparan sulfate by clinical strains of dengue virus serotype 1 using recombinant subviral particles

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dengue is the most important arthropod-borne viral disease in humans, with an estimated 3.6 billion people at risk for infection and more than 200 million infections per year. Identification of the cellular receptors for dengue virus (DV), the causative agent of dengue, is important toward understanding the pathogenesis of the disease. Heparan sulfate (HS) has been characterized as a DV receptor in multiple model systems, however the physiological relevance of these findings has been questioned by observations that flaviviruses, including DV, can undergo cell culture adaptation changes resulting in increased binding to HS. It thus remains unclear whether HS is utilized by clinical, non-cell culture-adapted strains of DV. To address this question, herein we describe a set of methodologies using recombinant subviral particles (RSPs) to determine the utilization of HS by clinical strains of DV serotype 1 (DV1). RSPs of clinically isolated strains with low cell culture passage histories were used to study HS interaction. Biochemically characterized RSPs showed dose-dependent binding to immobilized heparin, which could be competed by heparin and HS but not structurally related glycosaminoglycans chondroitin sulfate A and hyaluronic acid. The relevance of heparin and HS biochemical interactions was demonstrated by competition of RSP and DV binding to cells with soluble heparin and HS. Our results demonstrate that clinical strains of DV1 can specifically interact with heparin and HS. Together, these data support the possibility that HS on cell surfaces is utilized in the DV-human infection process.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins.

          The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The Economic Burden of Dengue

            Historically, dengue has been considered an unimportant public health problem because mortality rates were low and epidemics occurred only infrequently. In the years after World War II, great progress was made in controlling infectious diseases of all kinds, especially vector-borne diseases, and the war on infectious disease was declared won in the late 1960s.1 Coincident with this success in disease control was the economic recovery in some countries of Southeast Asia, and urban growth increased as people from rural areas migrated to the cities to find work. The lack of planning, inadequate housing, water, sewage, and waste management in these cities created ideal conditions for dengue viruses and their mosquito vector Aedes aegypti, both of which had been spread widely in the region during World War II, to thrive.2 The result was the emergence of epidemic dengue hemorrhagic fever. During the 1950s and 1960s, the disease was limited to a few countries in Southeast Asia, but as economic growth expanded, the cities and epidemic dengue also grew, because little effort was made to control the mosquito vector. In the 1970s and accelerating in the last two decades of the 20th century, epidemic dengue expanded regionally and globally. Epidemics increased in both frequency and magnitude, and the viruses became hyperendemic (cocirculation of multiple virus serotypes) in most major cities of the tropics. Despite this alarming emergence of a severe and fatal form of epidemic dengue, the disease was still considered a minor public health problem by policymakers. In 2012, dengue is the most important vector-borne viral disease of humans and likely more important than malaria globally in terms of morbidity and economic impact. The latest studies estimate 3.6 billion people living in areas of risk, over 230 million infections, millions of cases of dengue fever, over 2 million cases of the severe disease, and 21,000 deaths.3 In addition to the public health and economic costs, there is a major social impact in those countries where large epidemics occur, often disrupting primary care for hospitalized patients.4 Given the dramatic urban growth and lack of adequate surveillance for dengue in tropical developing countries in the past 50 years, it is likely that even these figures underestimate the true disease burden of dengue. Thus, ignored for many years, only recently has the potential magnitude of the dengue problem been acknowledged by policymakers and funding agencies. This acknowledgment has resulted in excellent progress in understanding dengue virus biology and development of dengue vaccines and antiviral drugs but not economic impact of the disease. As the pipeline of dengue vaccine candidates, a number of which are already in clinical trials, has grown, it has become apparent that vaccine access will require more and better studies on the actual cost of dengue to endemic communities. In recent years, many studies have been conducted in different Asian and American countries in attempts to measure the economic impact of dengue on a community. Although most have contributed valuable information on the subject, none has provided comprehensive data on the actual cost of dengue disease. The work by Halasa and others5 provides one of the best studies to date on that subject. Working in collaboration with the Puerto Rico Department of Health and the US Centers for Disease Control and Prevention Dengue Branch in Puerto Rico, the investigators conducted a comprehensive review of 100 laboratory-confirmed dengue patients who experienced the disease between July of 2008 and March of 2010. The study included both adults and children and hospitalized and ambulatory care patients. Records were reviewed for each patient, who was then subjected to a comprehensive interview about their illness and how it impacted their activities. The work by Halasa and others5 measured the cost, both direct and indirect, of dengue in six categories of cases and went to considerable effort to validate their data. The results, perhaps not surprisingly, show the economic burden of dengue in Puerto Rico to be very high. This study is the first study to show the societal distribution of the economic cost of dengue, with the individual household bearing the largest burden (48%) compared with only 24% by the government and 22% by insurance.5 The total annual cost of dengue between 2002 and 2010 was $46.45 million ($418 million during the 9-year period).5 Clearly, there is a need to conduct more comprehensive studies of this kind in other dengue-endemic countries of the world. These kinds of data are needed to allow policymakers and public health officials to make informed decisions on the cost efficacy of dengue control programs. The private sector also needs comprehensive economic analyses to guide decision-making in vaccines and antiviral drug development. Finally, international funding agencies require these kinds of data to establish priorities in public health funding. Studies of this kind will always have limitations, and this study was no exception. However, the work by Halasa and others5 clearly identified the most important limitations, such as recall bias and not being able to estimate the cost of tourism and deaths associated with dengue. The latter two limitations, however, would add to the overall cost of dengue, driving the cost even higher. The fact that the study was supported by a private vaccine manufacturer might raise questions about conflict of interest by some people. In my mind, however, this possibility is not an issue because of the detailed methodology used and the reputation of the Brandeis group as the leader in research on the economic impact of dengue.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga.

              A sulfated polysaccharide, named fucoidan, from the marine alga Cladosiphon okamuranus is comprised of carbohydrate units containing glucuronic acid and sulfated fucose residues. Here we found this compound potently inhibits dengue virus type 2 (DEN2) infection. Viral infection was inhibited when DEN2, but not other serotypes, was pretreated with fucoidan. A carboxy-reduced fucoidan derivative in which glucuronic acid was converted to glucose did not inhibit viral infection. Elimination of the sulfated function group from fucoidan significantly attenuated the inhibitory activity on DEN2 infection with <1% fucoidan. DEN2 particles bound exclusively to fucoidan, indicating that fucoidan interacts directly with envelope glycoprotein (EGP) on DEN2. Structure-based analysis suggested that Arg323 of DEN2 EGP, which is conformationally proximal to one of the putative heparin binding residues, Lys310, is critical for the interaction with fucoidan. In conclusion, both the sulfated group and glucuronic acid of fucoidan account for the inhibition of DEN2 infection.
                Bookmark

                Author and article information

                Journal
                8410979
                7967
                Virus Res
                Virus Res.
                Virus research
                0168-1702
                1872-7492
                12 June 2014
                22 May 2013
                September 2013
                01 September 2014
                : 176
                : 0
                : 69-77
                Affiliations
                [a ]Program in Applied Biological Sciences: Environmental Health, Chulabhorn Graduate Institute, Bangkok, Thailand
                [b ]Department of Biological Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States
                [c ]Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok, Thailand
                Author notes
                [* ]Corresponding author at: 77 Massachusetts Avenue, 76-461c, Cambridge, MA 02139, United States. Tel.: +1 617 258 9494; fax: +1 617 253 7498. rams@ 123456mit.edu , adaz@ 123456mit.edu (R. Sasisekharan)
                Article
                NIHMS585329
                10.1016/j.virusres.2013.04.017
                4145673
                23707399
                a80c33a4-9c0c-4c5d-8629-ac57d0bc0cb0
                © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

                History
                Categories
                Article

                Microbiology & Virology
                dengue,heparan sulfate,recombinant subviral particle,receptor
                Microbiology & Virology
                dengue, heparan sulfate, recombinant subviral particle, receptor

                Comments

                Comment on this article