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

• Published in: The 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
• Language: English
• 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
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.13-0145

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.