<i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes

Chronic conditions like type II diabetes (T2DM) have long been known to exacerbate many infectious diseases. For many arboviruses, including Zika virus (ZIKV), severe outcomes, morbidity and mortality usually only occur in patients with such pre-existing conditions. However, the effects of T2DM and...

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Main Authors: Sasha R. Azar, Rafael K. Campos, Ruimei Yun, Taylor Strange, Shannan L. Rossi, Kathryn A. Hanley, Nikos Vasilakis, Scott C. Weaver
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/4/665
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author Sasha R. Azar
Rafael K. Campos
Ruimei Yun
Taylor Strange
Shannan L. Rossi
Kathryn A. Hanley
Nikos Vasilakis
Scott C. Weaver
author_facet Sasha R. Azar
Rafael K. Campos
Ruimei Yun
Taylor Strange
Shannan L. Rossi
Kathryn A. Hanley
Nikos Vasilakis
Scott C. Weaver
author_sort Sasha R. Azar
collection DOAJ
description Chronic conditions like type II diabetes (T2DM) have long been known to exacerbate many infectious diseases. For many arboviruses, including Zika virus (ZIKV), severe outcomes, morbidity and mortality usually only occur in patients with such pre-existing conditions. However, the effects of T2DM and other pre-existing conditions on human blood (e.g., hypo/hyperinsulinemia, hyperglycemia and hyperlipidemia) that may impact infectivity of arboviruses for vectors is largely unexplored. We investigated whether the susceptibility of Aedes aegypti mosquitoes was affected when the mosquitoes fed on “diabetic” bloodmeals, such as bloodmeals composed of artificially glycosylated erythrocytes or those from viremic, diabetic mice (LEPRDB/DB). Increasing glycosylation of erythrocytes from hemoglobin A1c (HgbA1c) values of 5.5–5.9 to 6.2 increased the infection rate of a Galveston, Texas strain of Ae. aegypti to ZIKV strain PRVABC59 at a bloodmeal titer of 4.14 log10 FFU/mL from 0.0 to 40.9 and 42.9%, respectively. ZIKV was present in the blood of viremic LEPRDB/DB mice at similar levels as isogenic control C57BL/6J mice (3.3 log10 FFU/mL and 3.6 log10 FFU/mL, respectively. When mice sustained a higher ZIKV viremia of 4.6 log10 FFU/mL, LEPRDB/DB mice infected 36.3% of mosquitoes while control C57BL/6J mice with a viremia of 4.2 log10 FFU/mL infected only 4.1%. Additionally, when highly susceptible Ae. aegypti Rockefeller mosquitoes fed on homozygous LEPRDB/DB, heterozygous LEPRWT/DB, and control C57BL/6J mice with viremias of ≈ 4 log10 FFU/mL, 54%, 15%, and 33% were infected, respectively. In total, these data suggest that the prevalence of T2DM in a population may have a significant impact on ZIKV transmission and indicates the need for further investigation of the impacts of pre-existing metabolic conditions on arbovirus transmission.
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spelling doaj.art-2fb4f087b6624c1e9dab3ef1f87570072023-11-30T22:02:33ZengMDPI AGViruses1999-49152022-03-0114466510.3390/v14040665<i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II DiabetesSasha R. Azar0Rafael K. Campos1Ruimei Yun2Taylor Strange3Shannan L. Rossi4Kathryn A. Hanley5Nikos Vasilakis6Scott C. Weaver7Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0609, USADepartment of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0609, USADepartment of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-0610, USADepartment of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0609, USADepartment of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0609, USADepartment of Biology, New Mexico State University, Las Cruces, NM 88003, USADepartment of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0609, USADepartment of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-0610, USAChronic conditions like type II diabetes (T2DM) have long been known to exacerbate many infectious diseases. For many arboviruses, including Zika virus (ZIKV), severe outcomes, morbidity and mortality usually only occur in patients with such pre-existing conditions. However, the effects of T2DM and other pre-existing conditions on human blood (e.g., hypo/hyperinsulinemia, hyperglycemia and hyperlipidemia) that may impact infectivity of arboviruses for vectors is largely unexplored. We investigated whether the susceptibility of Aedes aegypti mosquitoes was affected when the mosquitoes fed on “diabetic” bloodmeals, such as bloodmeals composed of artificially glycosylated erythrocytes or those from viremic, diabetic mice (LEPRDB/DB). Increasing glycosylation of erythrocytes from hemoglobin A1c (HgbA1c) values of 5.5–5.9 to 6.2 increased the infection rate of a Galveston, Texas strain of Ae. aegypti to ZIKV strain PRVABC59 at a bloodmeal titer of 4.14 log10 FFU/mL from 0.0 to 40.9 and 42.9%, respectively. ZIKV was present in the blood of viremic LEPRDB/DB mice at similar levels as isogenic control C57BL/6J mice (3.3 log10 FFU/mL and 3.6 log10 FFU/mL, respectively. When mice sustained a higher ZIKV viremia of 4.6 log10 FFU/mL, LEPRDB/DB mice infected 36.3% of mosquitoes while control C57BL/6J mice with a viremia of 4.2 log10 FFU/mL infected only 4.1%. Additionally, when highly susceptible Ae. aegypti Rockefeller mosquitoes fed on homozygous LEPRDB/DB, heterozygous LEPRWT/DB, and control C57BL/6J mice with viremias of ≈ 4 log10 FFU/mL, 54%, 15%, and 33% were infected, respectively. In total, these data suggest that the prevalence of T2DM in a population may have a significant impact on ZIKV transmission and indicates the need for further investigation of the impacts of pre-existing metabolic conditions on arbovirus transmission.https://www.mdpi.com/1999-4915/14/4/665<i>Aedes aegypti</i>zika virustype II diabetesTGF-βimmunological cross-talk
spellingShingle Sasha R. Azar
Rafael K. Campos
Ruimei Yun
Taylor Strange
Shannan L. Rossi
Kathryn A. Hanley
Nikos Vasilakis
Scott C. Weaver
<i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes
Viruses
<i>Aedes aegypti</i>
zika virus
type II diabetes
TGF-β
immunological cross-talk
title <i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes
title_full <i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes
title_fullStr <i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes
title_full_unstemmed <i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes
title_short <i>Aedes aegypti</i> Shows Increased Susceptibility to Zika Virus via Both In Vitro and In Vivo Models of Type II Diabetes
title_sort i aedes aegypti i shows increased susceptibility to zika virus via both in vitro and in vivo models of type ii diabetes
topic <i>Aedes aegypti</i>
zika virus
type II diabetes
TGF-β
immunological cross-talk
url https://www.mdpi.com/1999-4915/14/4/665
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