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Updated: Aug 9, 2025
Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Zika virus spreads through infection of lymph node-resident macrophages
Glennys V Reynoso1, David N Gordon2, Anurag Kalia1
1Viral 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.
Abstract:
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.
Insights
Zika virus (ZIKV) spreads through lymph nodes by infecting resident macrophages, not migratory cells. These macrophages release the virus, initiating viremia and spread to other lymph nodes.
Area of Science:
- Virology
- Immunology
- Pathogen Dissemination
Background:
- Zika virus (ZIKV) dissemination mechanisms are not fully understood.
- Myeloid cell mobility, including monocytes and dendritic cells, is hypothesized to be key for ZIKV spread.
- The precise timing and cellular mechanisms of immune cell-mediated viral shuttling remain unclear.
Purpose of the Study:
- To elucidate the early steps of Zika virus (ZIKV) transit from the skin.
- To spatially map ZIKV infection dynamics in lymph nodes (LNs) over time.
- To investigate the role of immune cells in ZIKV dissemination to LNs and blood.
Main Methods:
- Spatially mapping ZIKV infection in lymph nodes at various time points post-infection.
- Analyzing the contribution of migratory immune cells versus sessile macrophages in viral transport.
- Assessing the sufficiency of CD169+ macrophage infection in initiating viremia.
Main Results:
- Contrary to existing hypotheses, migratory immune cells are not essential for ZIKV to reach LNs or the bloodstream.
- ZIKV rapidly infects sessile CD169+ macrophages within LNs.
- Infection of these resident CD169+ macrophages alone is sufficient to trigger viremia.
- Infected CD169+ macrophages release infectious ZIKV, facilitating spread to downstream LNs.
Conclusions:
- Resident CD169+ macrophages in lymph nodes play a critical role in the initial dissemination of ZIKV.
- The findings challenge the prevailing model of migratory immune cell-driven ZIKV spread.
- Lymph node macrophages represent a potential target for antiviral interventions against ZIKV.
