Zika Virus-Infected Monocyte Exosomes Mediate Cell-to-Cell Viral Transmission

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 2; p. 144
• Main Authors: Martínez-Rojas, Pedro Pablo, Monroy-Martínez, Verónica, Agredano-Moreno, Lourdes Teresa, Jiménez-García, Luis Felipe, Ruiz-Ordaz, Blanca H
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024
• Subjects: Autoimmunity; Biosynthesis; CD63 antigen; CD81 antigen; Cell activation; Cell differentiation; Cell interaction; Cell organelles; cell-to-cell viral transmission; Cytofluorometry; Dengue fever; Disease transmission; Exosomes; Extracellular Vesicles; Fever; Health aspects; human monocytes; Humans; Immune response; Infections; Microscopy; Monocytes; Mosquitoes; Nanoparticles; Neurological diseases; Pathogenesis; Proteins; small extracellular vesicles; Transmission electron microscopy; Ultracentrifugation; Ultraviolet radiation; Viral diseases; Viruses; West Nile virus; Zika Virus; Zika Virus Infection; Mexico; United States > US; cell-to-cell viral transmission; Zika virus; extracellular vesicles; human monocytes; small extracellular vesicles; exosomes
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13020144

Zika fever is a reemerging arthropod-borne viral disease; however, Zika virus (ZIKV) can be transmitted by other, non-vector means. Severe Zika fever is characterized by neurological disorders, autoimmunity, or congenital Zika syndrome. Monocytes are primary ZIKV targets in humans and, in response to infection, release extracellular vesicles like exosomes. Exosomes mediate intercellular communication and are involved in the virus's ability to circumvent the immune response, promoting pathological processes. This study aimed to evaluate the role of monocyte exosomes in cell-to-cell viral transmission. We isolated exosomes from ZIKV-infected monocytes (Mø exo ZIKV) by differential ultracentrifugation and identified them by nanoparticle tracking analysis; transmission electron microscopy; and CD63, CD81, TSG101, and Alix detection by cytofluorometry. Purified exosome isolates were obtained by uncoupling from paramagnetic beads or by treatment with UV radiation and RNase A. We found that Mø exo ZIKV carry viral RNA and E/NS1 proteins and that their interaction with naïve cells favors viral transmission, infection, and cell differentiation/activation. These data suggest that Mø exo ZIKV are an efficient alternative pathway for ZIKV infection. Knowledge of these mechanisms contributes to understanding the pathogenesis of severe disease and to the development of new vaccines and therapies.