Early cellular innate immune responses drive Zika viral persistence and tissue tropism in pigtail macaques

• Published in: Nature communications Vol. 9; no. 1; pp. 3371 - 11
• Main Authors: O’Connor, Megan A., Tisoncik-Go, Jennifer, Lewis, Thomas B., Miller, Charlene J., Bratt, Debra, Moats, Cassie R., Edlefsen, Paul T., Smedley, Jeremy, Klatt, Nichole R., Gale, Michael, Fuller, Deborah Heydenburg
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.08.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 49/88; 631/250/255/2514; 631/326/596/2553; 631/326/596/2555; 631/326/596/2557; 64; 82/1; Animals; Blood; Chemokine CCL2 - metabolism; Dendritic cells; Humanities and Social Sciences; Immunity, Innate - physiology; Immunology; Infections; Innate immunity; Lymph nodes; Macaca nemestrina - immunology; Macaca nemestrina - metabolism; Macaca nemestrina - virology; Males; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; multidisciplinary; Pathogenesis; Peripheral blood; Proteins; Science; Science (multidisciplinary); T cell receptors; Tropism; Vector-borne diseases; Viruses; Zika virus; Zika Virus - immunology; Zika Virus Infection - immunology; Zika Virus Infection - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05826-w

The immunological and virological events that contribute to the establishment of Zika virus (ZIKV) infection in humans are unclear. Here, we show that robust cellular innate immune responses arising early in the blood and tissues in response to ZIKV infection are significantly stronger in males and correlate with increased viral persistence. In particular, early peripheral blood recruitment of plasmacytoid dendritic cells and higher production of monocyte chemoattractant protein (MCP-1) correspond with greater viral persistence and tissue dissemination. We also identify non-classical monocytes as primary in vivo targets of ZIKV infection in the blood and peripheral lymph node. These results demonstrate the potential differences in ZIKV pathogenesis between males and females and a key role for early cellular innate immune responses in the blood in viral dissemination and ZIKV pathogenesis. The immune response to Zika virus is required to curtail the infection and avoid immunopathology, but may be involved in the associated pathophysiology. Here the authors show that viral persistence and tissue tropism is shaped by an early innate immune response in a pigtail macaque model of infection.