Abstract

The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution microscopic analysis allowed us to identify as targets of viral infection: skeletal muscle cells, cardiomyocytes, nervous system cells, renal tubular epithelium, lung parenchyma, and fibroblasts associated with connective tissue in the perichondrium and dermis. The virus replication was heaviest in muscle tissues. In all of these specimens, RT-PCR methods confirmed the presence of replicative intermediate and genomic YF RNA. This clearer characterization of cell targets in chicken embryos paves the way for future development of a new YF vaccine based on a new cell culture system.

Highlights

  • Since 1937, the vaccine against yellow fever has been produced in chicken embryos without any critical modification

  • Despite this highly available and effective vaccine, yellow fever remains an important cause of morbidity and mortality in tropical regions of Africa and South America, mainly by maintaining the sylvatic cycle

  • Yellow fever (YF) is a viral disease associated with a flavivirus infection that affects individuals in the tropical regions of South America and Sub-Saharan Africa

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Summary

Introduction

Yellow fever (YF) is a viral disease associated with a flavivirus infection that affects individuals in the tropical regions of South America and Sub-Saharan Africa. The course of the disease may be mild, subclinical, or abortive (with flu-like symptoms), or severe. Studies have described the pathology and pathogenesis of YF in fatal human cases, and in experimental infections of non-human primates, golden hamsters, and mice [3,4,5,6,7]. All these models can only provide information on YF pathology of fatal cases. There are no available models for the study of moderate, mild, and subclinical forms of YF [6]

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