Serotype-specific host responses in rhesus macaques after primary dengue challenge

Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, a...

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Published inThe American journal of tropical medicine and hygiene Vol. 89; no. 6; pp. 1043 - 1057
Main Authors Hickey, Andrew C, Koster, Jacob A, Thalmann, Claudia M, Hardcastle, Kathy, Tio, Phaik-Hooi, Cardosa, Mary J, Bossart, Katharine N
Format Journal Article
LanguageEnglish
Published United States The American Society of Tropical Medicine and Hygiene 01.12.2013
Subjects
Animals
Antibodies, Neutralizing - biosynthesis
Antibodies, Neutralizing - blood
Antibodies, Viral - biosynthesis
Antibodies, Viral - blood
Cercopithecus aethiops
Cytokines - blood
Dengue - immunology
Dengue - virology
Dengue virus
Dengue Virus - immunology
Female
Fibrin Fibrinogen Degradation Products - analysis
Fibrinogen - analysis
Hematologic Tests
Humans
Immunity, Humoral
Immunoglobulin G - biosynthesis
Immunoglobulin G - blood
Immunoglobulin M - biosynthesis
Immunoglobulin M - blood
Macaca mulatta
Male
Protein C - analysis
RNA, Viral - genetics
Severe Dengue - immunology
Severe Dengue - virology
Species Specificity
Vero Cells
Online AccessGet full text

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Abstract Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.
AbstractList Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo , rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.
Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo , rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.
Author Thalmann, Claudia M
Cardosa, Mary J
Koster, Jacob A
Tio, Phaik-Hooi
Hardcastle, Kathy
Bossart, Katharine N
Hickey, Andrew C
AuthorAffiliation Department of Microbiology, National Emerging Infectious Diseases Laboratories Institute, Laboratory Animal Science Center, Boston University, Boston, Massachusetts; Venture Technologies, Penang, Malaysia; Sentinext Therapeutics, Penang, Malaysia
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Snippet Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further...
SourceID pubmedcentral
proquest
crossref
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SourceType Open Access Repository
Aggregation Database
Index Database
StartPage 1043
SubjectTerms Animals
Antibodies, Neutralizing - biosynthesis
Antibodies, Neutralizing - blood
Antibodies, Viral - biosynthesis
Antibodies, Viral - blood
Cercopithecus aethiops
Cytokines - blood
Dengue - immunology
Dengue - virology
Dengue virus
Dengue Virus - immunology
Female
Fibrin Fibrinogen Degradation Products - analysis
Fibrinogen - analysis
Hematologic Tests
Humans
Immunity, Humoral
Immunoglobulin G - biosynthesis
Immunoglobulin G - blood
Immunoglobulin M - biosynthesis
Immunoglobulin M - blood
Macaca mulatta
Male
Protein C - analysis
RNA, Viral - genetics
Severe Dengue - immunology
Severe Dengue - virology
Species Specificity
Vero Cells
Title Serotype-specific host responses in rhesus macaques after primary dengue challenge
URI https://www.ncbi.nlm.nih.gov/pubmed/24062475
https://search.proquest.com/docview/1465864323
https://search.proquest.com/docview/1647024038
https://pubmed.ncbi.nlm.nih.gov/PMC3854881
Volume 89
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