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Breastfeeding by chikungunya virus-infected dams confers resistance to challenge in the offspring

Published:December 13, 2022DOI:https://doi.org/10.1016/j.trsl.2022.12.001

      Abstract

      Vertical transmission of Chikungunya virus (CHIKV) has been reported in humans, but the transmission routes have not been completely understood, and experimental animal models are needed to enable detailed investigation of the transmission and pathogenesis of congenital infections. The intertwining of immune response and virus components at the gestation/breastfeeding interfaces between mother and fetus/newborn may have effects during the offspring development. An experimental model of CHIKV was established by infecting pregnant BALB/c female mice that enabled confirmation that dams inoculated up to the 10th gestational day transmit CHIKV transplacentally to approximately 8.4% of the fetuses, resulting in severe teratogenic effects. CHIKV neutralizing antibodies were detected in sera from adult mice born to healthy females and breastfed by CHIKV-infected dams, while no neutralization was detected in sera from animals born to CHIKV-infected dams. Moreover, adult mice born to healthy dams and cross-fostered for breastfeeding by CHIKV-infected dams were resistant to challenge with CHIKV on the 90th day after birth. The animals also had reduced viral loads in brain and spleen as compared to controls. There was expression of fluorescent CHIKV non-structural protein, and detection of viral RNA by RT-PCR in breast tissue from infected dams. CHIKV RNA and proteins were also detected in breast milk retrieved from the stomachs of recently fed newborns. The experimental results were also complemented by the finding of CHIKV RNA in 6% of colostrum samples from healthy lactating women in a CHIKV-endemic area. Breastfeeding induces immune protection to challenge with CHIKV in mice.

      Abbreviations:

      CHIKV (chikungunya virus), FBS (fetal bovine serum), rCHIKV-mCherry (recombinant chikungunya virus expressing mCherry), UV (ultraviolet), RNA (ribonucleic acid), cDNA (complementary DNA), PRNT (plaque reduction neutralization assay), PFU (plaque forming unit), DAPI (Diamidino-2-phenylindole), NaCl (sodium chloride), EDTA (ethylenediamine tetra-acetic), RT-qPCR (reverse transcription – quantitative polymerase chain reaction), DTT (dithiothreitol), SDS-PAGE (sodium dodecyl sulphate–polyacrylamide gel electrophoresis), HRP (horseradish peroxidase), IgG (immunoglobulin G), kDa (kilodalton), nsP1234 (nonstructural polyprotein 1234), C-E3-E2-6K-E1 (structural polyprotein capsid-envelope 1-envelope 2-6K-envelope 1), E1/E2 (envelope proteins 1 and 2), rE2 (recombinant envelop protein 2)
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