Modelling the impact of antibody-dependent enhancement on disease severity of Zika virus and dengue virus sequential and co-infection

• Autores: Tang, Biao; Xiao, Yanni; Sander, Beate; Kulkarni, Manisha A.; Wu, Jianhong; Miretti, Marcos Mateo
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ANTIBODY-DEPENDENT ENHANCEMENT; DENV; MATHEMATICAL MODEL; PARAMETER ESTIMATION; VIRAL DYNAMICS; ZIKV
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Human infections with viruses of the genus Flavivirus, including dengue virus (DENV) and Zika virus (ZIKV), are of increasing global importance. Owing to antibody-dependent enhancement (ADE), secondary infection with one Flavivirus following primary infection with another Flavivirus can result in a significantly larger peak viral load with a much higher risk of severe disease. Although several mathematical models have been developed to quantify the virus dynamics in the primary and secondary infections of DENV, little progress has been made regarding secondary infection of DENV after a primary infection of ZIKV, or DENV-ZIKV co-infection. Here, we address this critical gap by developing compartmental models of virus dynamics. We first fitted the models to published data on dengue viral loads of the primary and secondary infections with the observation that the primary infection reaches its peak much more gradually than the secondary infection. We then quantitatively show that ADE is the key factor determining a sharp increase/decrease of viral load near the peak time in the secondary infection. In comparison, our simulations of DENV and ZIKV co-infection (simultaneous rather than sequential) show that ADE has very limited influence on the peak DENV viral load. This indicates pre-existing immunity to ZIKV is the determinant of a high level of ADE effect. Our numerical simulations show that (i) in the absence of ADE effect, a subsequent co-infection is beneficial to the second virus; and (ii) if ADE is feasible, then a subsequent co-infection can induce greater damage to the host with a higher peak viral load and a much earlier peak time for the second virus, and for the second peak for the first virus.
Fil: Tang, Biao. University of York; Reino Unido. University of Toronto; Canadá
Fil: Xiao, Yanni. Xi'an Jiaotong University; China
Fil: Sander, Beate. University of Toronto; Canadá
Fil: Kulkarni, Manisha A.. University of Ottawa; Canadá
Fil: Wu, Jianhong. University of York; Reino Unido
Fil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentina