Large-particle aerosol exposure to the Bangladesh or Malaysia strain of Nipah virus results in markedly divergent disease presentation in African Green Monkeys

Sep 29, 2026

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Nipah virus causes severe respiratory and neurological disease in humans, and two major viral lineages show different clinical presentations. This study tested strain-specific differences by exposing African green monkeys to either the Malaysia (NiV-M) or Bangladesh (NiV-B) strain via a large-particle aerosol route. NiV-M produced 27% fatality, whereas NiV-B produced 75% fatality with rapid respiratory decline and systemic dissemination. Survivors with NiV-M developed stronger early humoral responses, while NiV-B survivors showed weaker delayed immunity. Across both strains, non-survivors exhibited elevated pro-inflammatory cytokines, thrombocytopenia, and multi-organ dysfunction; imaging and pathology further contrasted neuroinflammation/vasculitis and pulmonary pathology with distinct vascular injury and coagulopathy patterns.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

Abstract

Strain-specific outcomes

Humoral responses

Inflammation, thrombocytopenia, and organ dysfunction

Imaging and histopathology

OPEN ACCESS Citation: Cong Y, Bearss J, Mani V, Lackemeyer M, Pahar B, Huzella LM, et al. (2025) Large-particle aerosol exposure to the Bangladesh or Malaysia strain of Nipah virus results in markedly divergent disease presentation in African Green Monkeys. PLoS Pathog 21(12): e1013835. [https://doi](https://doi). org/10.1371/journal.ppat.1013835 Editor: Alexander Bukreyev, University of Texas Medical Branch / Galveston National Laboratory, UNITED STATES OF AMERICA Received: August 28, 2025 Accepted: December 18, 2025 Published: December 29, 2025 Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data availability statement: All relevant data are within the manuscript and its Supporting information files. RESEARCH ARTICLE Large-particle aerosol exposure to the Bangladesh or Malaysia strain of Nipah virus results in markedly divergent disease presentation in African Green Monkeys Yu Cong1, Jeremy Bearss1, Venkatesh Mani1, Matthew Lackemeyer1, Bapi Pahar1, Louis M. Huzella1, Erin Kollins1, Steve Mazur1, Saurabh Dixit1, Sanae Lembirik1, David Drawbaugh1, Philip J. Sayre1, Joseph Laux1, Jeffrey Solomon2, Dima A. Hammoud3, Ji Hyun Lee4, Claudia Calcagno1, Russ Byrum1, Marisa St. Claire1, Jiro Wada1, Vincent Munster5, Michael R. Holbrook1* 1 Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America, 2 Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America, 3 Clinical Center, Center for Infectious Disease Imaging, National Institutes of Health, Bethesda, Maryland, United States of America, 4 Clinical Center, Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland, United States of America, 5 Virus Ecology Unit, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America * [michael.holbrook@nih.gov](michael.holbrook@nih.gov) Abstract Nipah virus (NiV), a highly pathogenic zoonotic paramyxovirus, causes severe respiratory and neurological disease in humans, with a case-fatality rate around 60% . Descriptions of cases in the clinical setting suggest that the two primary lineages of NiV cause disease with different presentations and outcomes. To definestrain-specific differences in disease progression and host responses, African green monkeys were exposed to either the Malaysia (NiV-M) or Bangladesh (NiV-B) strain using a large-particle aerosol exposure. NiV-M infection resulted in a fatality rate of 27%, while NiV-B infection led to a 75% fatality rate characterized by rapid respiratory decline and systemic viral dissemination. Among survivors, NiV-M–infected animals mounted robust immunoglobulin M, immunoglobulin G, and neutralizing antibody responses, whereas NiV-B survivors exhibited weaker and delayed humoral responses. Non-survivors of both strains showed elevated pro-inflammatory cytokines, thrombocytopenia, and multi-organ dysfunction. Imaging showed that NiV-M infection was associated with neuroinflammation and systemic vasculitis, while NiV-B infection caused progressive pulmonary pathology. Histopathological analysis confirmed widespread vasculitis and encephalitis in animals with NiV-M infection and diffuse pulmonary hemorrhage and fibrin thrombi, consistent with vascular injury and coagulopathy, in animals with NiV-B infection. Cytokine profiling and flow cytometry showed a more intense and dysregulated immune response to NiV-B infection. Fatal PLOS Pathogens | [https://doi.org/10.1371/journal.ppat.1013835](https://doi.org/10.13

FAQs

How were African green monkeys exposed to Nipah virus strains in this study?

Monkeys were exposed to either the Malaysia (NiV-M) or Bangladesh (NiV-B) strain using a large-particle aerosol exposure approach.

What fatality rates were observed for NiV-M versus NiV-B?

NiV-M infection resulted in 27% fatality, while NiV-B infection led to 75% fatality characterized by rapid respiratory decline and systemic viral dissemination.

How did immune responses differ between survivors of the two strains?

NiV-M survivors mounted robust IgM, IgG, and neutralizing antibody responses, whereas NiV-B survivors exhibited weaker and delayed humoral responses.

Sep 29, 2026

Uploaded by moss~