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  1. Article ; Online: Viral evolution and epidemiology.

    Leitmeyer, Katrin / Rico-Hesse, Rebeca

    Current opinion in infectious diseases

    2015  Volume 10, Issue 5, Page(s) 367–371

    Abstract: This review highlights recent research on viral evolution and its use towards understanding disease pathogenesis and epidemiology. The development of techniques such as enzymatic amplification of viral genomes and automated sequencing has led to a ... ...

    Abstract This review highlights recent research on viral evolution and its use towards understanding disease pathogenesis and epidemiology. The development of techniques such as enzymatic amplification of viral genomes and automated sequencing has led to a dramatic increase in the amount of sequence information from clinical samples. These sequences (RNA or DNA, or the amino acids they encode) have been compared by complex computer algorithms to generate evolutionary trees or phylogenies of natural virus variants, which can sometimes be used to correlate viral genotype with phenotype. Understanding the rates and types of evolution that occur during the transmission of viruses has considerable impact on the design of methods for the control of virus diseases.
    Language English
    Publishing date 2015-08-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645085-4
    ISSN 1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
    ISSN (online) 1473-6527 ; 1535-3877
    ISSN 0951-7375 ; 1355-834X
    DOI 10.1097/00001432-199710000-00008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Dengue virus markers of virulence and pathogenicity.

    Rico-Hesse, Rebeca

    Future virology

    2009  Volume 4, Issue 6, Page(s) 581

    Abstract: The increased spread of dengue fever and its more severe form, dengue hemorrhagic fever, have made the study of the mosquito-borne dengue viruses that cause these diseases a public health priority. Little is known about how or why the four different ( ... ...

    Abstract The increased spread of dengue fever and its more severe form, dengue hemorrhagic fever, have made the study of the mosquito-borne dengue viruses that cause these diseases a public health priority. Little is known about how or why the four different (serotypes 1-4) dengue viruses cause pathology in humans only, and there have been no animal models of disease to date. Therefore, there are no vaccines or antivirals to prevent or treat infection and mortality rates of dengue hemorrhagic fever patients can reach up to 20%. Cases occur mainly in tropical zones within developing countries worldwide, and control measures have been limited to the elimination of the mosquito vectors. Thus, it is imperative that we develop new methods of studying dengue virus pathogenicity. This article presents new approaches that may help us to understand dengue virus virulence and the specific mechanisms that lead to dengue fever and severe disease.
    Language English
    Publishing date 2009-06-23
    Publishing country England
    Document type Journal Article
    ISSN 1746-0794
    ISSN 1746-0794
    DOI 10.2217/fvl.09.51
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dengue virus tropism in humanized mice recapitulates human dengue fever.

    Mota, Javier / Rico-Hesse, Rebeca

    PloS one

    2011  Volume 6, Issue 6, Page(s) e20762

    Abstract: Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem ... ...

    Abstract Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infection in human cells in bone marrow, spleen and blood. Cytokines and chemokines were secreted by these human cells into the mouse bloodstream. We demonstrated that the pathology of dengue virus infection in these mice follows that reported in human patients, making this the first valid and relevant model for studying dengue fever pathogenesis in humans.
    MeSH term(s) Animals ; Chemokines/biosynthesis ; Dengue/virology ; Dengue Virus/physiology ; Disease Models, Animal ; Host Specificity/physiology ; Humans ; Lymphocytes/virology ; Mice ; Species Specificity
    Chemical Substances Chemokines
    Language English
    Publishing date 2011-06-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0020762
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Dengue virus evolution and virulence models.

    Rico-Hesse, Rebeca

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2007  Volume 44, Issue 11, Page(s) 1462–1466

    Abstract: Dengue virus transmission has increased dramatically in the past 2 decades, making this virus one of the most important mosquito-borne human pathogens. The emergence of dengue hemorrhagic fever in most tropical countries has made its control a public ... ...

    Abstract Dengue virus transmission has increased dramatically in the past 2 decades, making this virus one of the most important mosquito-borne human pathogens. The emergence of dengue hemorrhagic fever in most tropical countries has made its control a public health priority, but no vaccines or treatments exist. Little is understood about dengue virus pathogenesis, because no other animals develop symptoms of disease, and research, therefore, has been limited to studies involving patients. Although epidemiologic and evolutionary studies have pointed to host and viral factors in determining disease outcome, only recently developed models could prove the importance of viral genotypes in causing severe epidemics. The influence of host immune status and mosquito vectorial capacity are also being tested in mathematical models to determine virus population dynamics. Therefore, new technologies are allowing us to better understand how specific virus variants cause more disease than others, and these virus variants should be targeted for detection, control, and treatment.
    MeSH term(s) Animals ; Dengue Virus/classification ; Dengue Virus/genetics ; Dengue Virus/pathogenicity ; Disease Models, Animal ; Evolution, Molecular ; Humans ; Phylogeny ; Severe Dengue/epidemiology ; Severe Dengue/transmission ; Severe Dengue/virology ; Virulence
    Language English
    Publishing date 2007-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1086/517587
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Humanized mice show clinical signs of dengue fever according to infecting virus genotype.

    Mota, Javier / Rico-Hesse, Rebeca

    Journal of virology

    2009  Volume 83, Issue 17, Page(s) 8638–8645

    Abstract: We demonstrated that the infection of humanized NOD-scid IL2r gamma(null) mice with different strains (representing the four genotypes) of dengue virus serotype 2 (DEN-2) can induce the development of human-like disease, including fever, viremia, ... ...

    Abstract We demonstrated that the infection of humanized NOD-scid IL2r gamma(null) mice with different strains (representing the four genotypes) of dengue virus serotype 2 (DEN-2) can induce the development of human-like disease, including fever, viremia, erythema, and thrombocytopenia. Newborn mice were irradiated and received transplants by intrahepatic inoculation of human cord blood-derived hematopoietic progenitor cells (CD34(+)). After 6 weeks, mouse peripheral blood was tested by flow cytometry to determine levels of human lymphocytes (CD45(+) cells); rates of reconstitution ranged from 16 to 80% (median, 52%). Infection (with approximately 10(6) PFU, the equivalent of a mosquito bite) of these humanized mice with eight low-passage-number strains produced a high viremia extending to days 12 to 18 postinfection. We observed a significant decrease in platelets at day 10 in most of the mice and an increase in body temperature (fever) and erythema (rash) in comparison with humanized mice inoculated with cell culture medium only. Comparison of Southeast (SE) Asian and other genotype viruses (American, Indian, and West African) in this model showed significant differences in magnitude and duration of viremia and rash, with the SE Asian viruses always being highest. Indian genotype viruses produced lower viremias and less thrombocytopenia than the others, and West African (sylvatic) viruses produced the shortest periods of viremia and the lowest rash measurements. These results correlate with virulence and transmission differences described previously for primary human target cells and whole mosquitoes and may correlate with epidemiologic observations around the world. These characteristics make this mouse model ideal for the study of dengue pathogenesis and the evaluation of vaccine attenuation and antivirals.
    MeSH term(s) Animals ; Dengue/pathology ; Dengue/physiopathology ; Dengue/virology ; Dengue Virus/genetics ; Dengue Virus/pathogenicity ; Disease Models, Animal ; Erythema/etiology ; Fever/etiology ; Genotype ; Humans ; Lymphocytes/immunology ; Mice ; Mice, SCID ; Severity of Illness Index ; Stem Cell Transplantation ; Thrombocytopenia/etiology ; Time Factors ; Viremia/etiology ; Virulence
    Language English
    Publishing date 2009-06-17
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00581-09
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Dengue virus tropism in humanized mice recapitulates human dengue fever.

    Javier Mota / Rebeca Rico-Hesse

    PLoS ONE, Vol 6, Iss 6, p e

    2011  Volume 20762

    Abstract: Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem ... ...

    Abstract Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infection in human cells in bone marrow, spleen and blood. Cytokines and chemokines were secreted by these human cells into the mouse bloodstream. We demonstrated that the pathology of dengue virus infection in these mice follows that reported in human patients, making this the first valid and relevant model for studying dengue fever pathogenesis in humans.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Microevolution and virulence of dengue viruses.

    Rico-Hesse, Rebeca

    Advances in virus research

    2003  Volume 59, Page(s) 315–341

    Abstract: The evolution of dengue viruses has had a major impact on their virulence for humans and on the epidemiology of dengue disease around the world. Although antigenic and genetic differences in virus strains had become evident, it is mainly due to the lack ... ...

    Abstract The evolution of dengue viruses has had a major impact on their virulence for humans and on the epidemiology of dengue disease around the world. Although antigenic and genetic differences in virus strains had become evident, it is mainly due to the lack of animal models of disease that has made it difficult to detect differences in virulence of dengue viruses. However, phylogenetic studies of many different dengue virus samples have led to the association between specific genotypes (within serotypes) and the presentation of more or less severe disease. Currently, dengue viruses can be classified as being of epidemiologically low, medium, or high impact; i.e., some viruses may remain in sylvatic cycles of little or low transmissibility to humans, others produce dengue fever (DF) only, and some genotypes have been associated with the potential to cause the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in addition to DF. Although the factors that contribute to dengue virus epidemiology are complex, studies have suggested that specific viral structures may contribute to increased replication in human target cells and to increased transmission by the mosquito vector; however, the immune status and possibly the genetic background of the host are also determinants of virulence or disease presentation. As to the question of whether dengue viruses are evolving toward virulence as they continue to spread throughout the world, phylogenetic and epidemiological analyses suggest that the more virulent genotypes are now displacing those that have lower epidemiological impact; there is no evidence for the transmission of antigenically aberrant, new strains.
    MeSH term(s) Animals ; Dengue/epidemiology ; Dengue/transmission ; Dengue/virology ; Dengue Virus/classification ; Dengue Virus/genetics ; Dengue Virus/pathogenicity ; Evolution, Molecular ; Genetic Variation ; Humans ; Phylogeny ; Serotyping ; Virulence
    Language English
    Publishing date 2003-12-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 195-8
    ISSN 1557-8399 ; 0065-3527
    ISSN (online) 1557-8399
    ISSN 0065-3527
    DOI 10.1016/s0065-3527(03)59009-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Variation in vector competence for dengue viruses does not depend on mosquito midgut binding affinity.

    Cox, Jonathan / Brown, Heidi E / Rico-Hesse, Rebeca

    PLoS neglected tropical diseases

    2011  Volume 5, Issue 5, Page(s) e1172

    Abstract: Background: Dengue virus genotypes of Southeast Asian origin have been associated with higher virulence and transmission compared to other genotypes of serotype 2 (DEN-2). We tested the hypothesis that genetic differences in dengue viruses may result in ...

    Abstract Background: Dengue virus genotypes of Southeast Asian origin have been associated with higher virulence and transmission compared to other genotypes of serotype 2 (DEN-2). We tested the hypothesis that genetic differences in dengue viruses may result in differential binding to the midgut of the primary vector, Aedes aegypti, resulting in increased transmission or vectorial capacity.
    Methodology/principal finding: Two strains of each of the four DEN-2 genotypes (Southeast Asian, American, Indian, and West African) were tested to determine their binding affinity for mosquito midguts from two distinct populations (Tapachula, Chiapas, Mexico and McAllen, Texas, USA). Our previous studies demonstrated that Southeast Asian viruses disseminated up to 65-fold more rapidly in Ae. aegypti from Texas and were therefore more likely to be transmitted to humans. Results shown here demonstrate that viruses from all four genotypes bind to midguts at the same rate, in a titer-dependent manner. In addition, we show population differences when comparing binding affinity for DEN-2 between the Tapachula and McAllen mosquito colonies.
    Conclusions: If midgut binding potential is the same for all DEN-2 viruses, then viral replication differences in these tissues and throughout the mosquito can thus probably explain the significant differences in dissemination and vector competence. These conclusions differ from the established paradigms to explain mosquito barriers to infection, dissemination, and transmission.
    MeSH term(s) Aedes/virology ; Animals ; Dengue/transmission ; Dengue Virus/classification ; Dengue Virus/genetics ; Dengue Virus/isolation & purification ; Dengue Virus/physiology ; Disease Vectors ; Gastrointestinal Tract/virology ; Genotype ; Humans ; Mexico ; RNA, Viral/genetics ; Texas ; Virulence ; Virus Attachment
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2011-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2727
    ISSN (online) 1935-2735
    ISSN 1935-2727
    DOI 10.1371/journal.pntd.0001172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Variation in vector competence for dengue viruses does not depend on mosquito midgut binding affinity.

    Jonathan Cox / Heidi E Brown / Rebeca Rico-Hesse

    PLoS Neglected Tropical Diseases, Vol 5, Iss 5, p e

    2011  Volume 1172

    Abstract: Dengue virus genotypes of Southeast Asian origin have been associated with higher virulence and transmission compared to other genotypes of serotype 2 (DEN-2). We tested the hypothesis that genetic differences in dengue viruses may result in differential ...

    Abstract Dengue virus genotypes of Southeast Asian origin have been associated with higher virulence and transmission compared to other genotypes of serotype 2 (DEN-2). We tested the hypothesis that genetic differences in dengue viruses may result in differential binding to the midgut of the primary vector, Aedes aegypti, resulting in increased transmission or vectorial capacity.Two strains of each of the four DEN-2 genotypes (Southeast Asian, American, Indian, and West African) were tested to determine their binding affinity for mosquito midguts from two distinct populations (Tapachula, Chiapas, Mexico and McAllen, Texas, USA). Our previous studies demonstrated that Southeast Asian viruses disseminated up to 65-fold more rapidly in Ae. aegypti from Texas and were therefore more likely to be transmitted to humans. Results shown here demonstrate that viruses from all four genotypes bind to midguts at the same rate, in a titer-dependent manner. In addition, we show population differences when comparing binding affinity for DEN-2 between the Tapachula and McAllen mosquito colonies.If midgut binding potential is the same for all DEN-2 viruses, then viral replication differences in these tissues and throughout the mosquito can thus probably explain the significant differences in dissemination and vector competence. These conclusions differ from the established paradigms to explain mosquito barriers to infection, dissemination, and transmission.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 570
    Language English
    Publishing date 2011-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Models of dengue virus infection.

    Bente, Dennis A / Rico-Hesse, Rebeca

    Drug discovery today. Disease models

    2007  Volume 3, Issue 1, Page(s) 97–103

    Abstract: The need for models of dengue disease has reached a pinnacle as the transmission of this mosquito-borne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; ... ...

    Abstract The need for models of dengue disease has reached a pinnacle as the transmission of this mosquito-borne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; this is owing to the fact that only humans show signs of disease. In the past 5 years, research has better identified the initial target cells of infection, and this has led to the development of models of infection in primary human cell cultures. Mouse-human chimeras, containing these target cells, have also led to progress in developing animal models. These advances should soon end the stalemate in testing antivirals and vaccine preparations that had necessarily been done in incomplete or irrelevant models.
    Language English
    Publishing date 2007-12-06
    Publishing country Netherlands
    Document type Journal Article
    ISSN 1740-6757
    ISSN 1740-6757
    DOI 10.1016/j.ddmod.2006.03.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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