Zika virus spreads through infection of lymph node-resident macrophages
Glennys V. Reynoso,
David N. Gordon,
Anurag Kalia,
Cynthia C. Aguilar,
Courtney S. Malo,
Maya Aleshnick,
Kimberly A. Dowd,
Christian R. Cherry,
John P. Shannon,
Sophia M. Vrba,
Autumn C. Holmes,
Yael Alippe,
Sonia Maciejewski,
Kenichi Asano,
Michael S. Diamond,
Theodore C. Pierson,
Heather D. Hickman
Affiliations
Glennys V. Reynoso
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
David N. Gordon
Viral Pathogenesis Section, Laboratory of Viral Diseases (LVD), NIAID, NIH, Bethesda, MD, USA
Anurag Kalia
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
Cynthia C. Aguilar
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
Courtney S. Malo
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
Maya Aleshnick
Viral Pathogenesis Section, Laboratory of Viral Diseases (LVD), NIAID, NIH, Bethesda, MD, USA
Kimberly A. Dowd
Viral Pathogenesis Section, Laboratory of Viral Diseases (LVD), NIAID, NIH, Bethesda, MD, USA
Christian R. Cherry
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
John P. Shannon
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
Sophia M. Vrba
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA
Autumn C. Holmes
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Yael Alippe
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Sonia Maciejewski
Viral Pathogenesis Section, Laboratory of Viral Diseases (LVD), NIAID, NIH, Bethesda, MD, USA
Kenichi Asano
Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan
Michael S. Diamond
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA
Theodore C. Pierson
Viral Pathogenesis Section, Laboratory of Viral Diseases (LVD), NIAID, NIH, Bethesda, MD, USA
Heather D. Hickman
Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA; Corresponding author
Summary: To disseminate through the body, Zika virus (ZIKV) is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, the timing and mechanisms underlying shuttling of the virus by immune cells remains unclear. To understand the early steps in ZIKV transit from the skin, at different time points, we spatially mapped ZIKV infection in lymph nodes (LNs), an intermediary site en route to the blood. Contrary to prevailing hypotheses, migratory immune cells are not required for the virus to reach the LNs or blood. Instead, ZIKV rapidly infects a subset of sessile CD169+ macrophages in the LNs, which release the virus to infect downstream LNs. Infection of CD169+ macrophages alone is sufficient to initiate viremia. Overall, our experiments indicate that macrophages that reside in the LNs contribute to initial ZIKV spread. These studies enhance our understanding of ZIKV dissemination and identify another anatomical site for potential antiviral intervention.
