Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients: Prolonged RNA Detection in Whole Blood

• Type of Material: Article
• Authors: Hana M El Sahly, Baylor College of Medicine; Rodion Gorchakov, Baylor College of Medicine; Lilin Lai, Emory University; Muktha S Natrajan, Emory University; Shital M Patel, Baylor College of Medicine; Robert L Atmar, Baylor College of Medicine; Wendy A Keitel, Baylor College of Medicine; Daniel F Hoft, St Louis University; Jill Barrett, Emmes Corporation; Jason Bailey, Emmes Corporation; Srilatha Edupuganti, Emory University; Vanessa Raabe, Emory University; Henry Wu, Emory University; Jessica Fairley, Emory University; Nadine Rouphael, Emory University; Kristy O Murray, Baylor College of Medicine; Mark Mulligan, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2018.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/ofid/ofy352
• Title of Journal or Parent Work: Open Forum Infectious Diseases
• ISSN: 2328-8957
• Volume: 6
• Issue: 1
• Start Page: ofy352
• End Page: ofy352
• Grant/Funding Information: Additional support was provided to M.J.M. by the Georgia Research Alliance and to V.R. by T32AI074492 from the National Institute of Allergy and Infectious Diseases.; The National Institutes of Allergy and Infectious Diseases at the National Institutes of Health provided contract funding for this project to the Vaccine and Treatment Evaluation Units at Baylor College of Medicine (HHSN272201300015I), Emory University (HHSN272201300018I), St. Louis University (HHSN27220130021I), and Emmes Corporation (HHSN272201500002C).
• Keywords: diagnostics; SECONDARY; Microbiology; IGG; TERRITORIES; Infectious Diseases; Life Sciences & Biomedicine; Zika; Immunology; Science & Technology; RESPONSES; cell-mediated immune response; DENGUE; serologic response; STATES; dengue
• Research Categories: Health Sciences, Immunology; Biology, Cell; Biology, Microbiology

Abstract

Background. Clinical, virologic, and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods. US subjects with suspected ZIKV infection were enrolled. Clinical data and specimens were prospectively collected for ZIKV RNA detection and serologic and cellular assays. Confirmed ZIKV infection (cases) and ZIKV-negative (controls) subjects were compared. Dengue-experienced and dengue-naive cases were also compared. Results. We enrolled 45 cases and 14 controls. Commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%), and arthralgia (82.2% and 54.5%), respectively. The sensitivity (94%) and duration of infection detection (80% positivity at 65-79 days after disease onset) by polymerase chain reaction were highest in whole-blood specimens. ZIKV-neutralizing antibodies had a half-life of 105 days and were significantly higher in dengue virus- experienced cases than naive ones (P = .046). In intracellular cytokine staining assays, the ZIKV proteins targeted most often by peripheral blood mononuclear cells from cases were structural proteins C and E for CD4+ T cells and nonstructural proteins NS3, NS5, and NS4B for CD8+ T cells. Conclusions. ZIKV RNA detection was more frequent and prolonged in whole-blood specimens. Immunoglobulin G (IgG) and neutralizing antibodies, but not IgM, were influenced by prior dengue infection. Robust cellular responses to E and nonstructural proteins have potential vaccine development implications.