A Human Skin Model for Assessing the Arboviral Infections

Autor: Allen T. Esterly, Megan G. Lloyd, Prashant Upadhyaya, Jennifer F. Moffat, Saravanan Thangamani
Rok vydání: 2022
Předmět:
DOI: 10.1101/2022.02.17.22271132
Popis: Arboviruses such as flaviviruses and alphaviruses cause a significant human healthcare burden on the global scale. Transmission of these viruses occurs during human blood feeding at the mosquito-skin interface. Not only do pathogen immune evasion strategies influence the initial infection and replication of pathogens delivered, but arthropod salivary factors also influence transmission foci. In-vitro cell cultures do not provide an adequate environment to study complex interactions between viral, mosquito, and host factors. To address this need for a whole tissue system, we describe a proof-of-concept model for arbovirus infection using adult human skin ex vivo with Zika virus (flavivirus) and Mayaro virus (alphavirus). Replication of these viruses in human skin was observed up to 4 days post-infection. Egressed viruses could be detected in the culture media as well. Antiviral and pro-inflammatory genes, including chemoattractant chemokines, were expressed in infected tissue. Immunohistochemical analysis showed the presence of virus in the skin tissue at 4 days post-infection. This model will be useful to further investigate: 1) the immediate molecular mechanisms of arbovirus infection in human skin, and 2) the influence of arthropod salivary molecules during initial infection of arboviruses in a more physiologically relevant system.
Databáze: OpenAIRE