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

2019 Jan

Journal Article

Sahly, H.M.El; Gorchakov, R.; Lai, L.; Natrajan, M.S.; Patel, S.M.; Atmar, R.L.; Keitel, W.A.; Hoft, D.F.; Barrett, J.; Bailey, J.; Edupuganti, S.; Raabe, V.; Wu, H.M.; Fairley, J.; Rouphael, N.; Murray, K.O.; Mulligan, M.J.

Open Forum Infect Dis






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-naïve 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 naïve ones ( = .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.

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