Authors

    Language

    English

    Publication Date

    1-1-2025

    Journal

    PLoS One

    DOI

    10.1371/journal.pone.0330631

    PMID

    40892760

    PMCID

    PMC12404477

    PubMedCentral® Posted Date

    9-2-2025

    PubMedCentral® Full Text Version

    Post-print

    Abstract

    Elephant endotheliotropic herpesviruses (EEHVs) cause EEHV hemorrhagic disease (EEHV-HD), an acute, multisystemic, often fatal hemorrhagic syndrome with profound implications for elephant population growth and sustainability. A greater understanding of the pathogenesis of EEHV-HD is essential to elucidate susceptibility and develop tools for disease management and prevention. This study utilized RNAscope® in situ hybridization (ISH) to detect EEHV1A DNA polymerase and terminase genes in archival tissues (heart, lung, tongue, spleen, liver, kidney, lymph node, stomach, small intestine, large intestine, salivary gland, and brain or spinal cord) from Asian elephants (Elephas maximus; n = 12) that died of EEHV-HD to determine and describe tissue and cellular tropism of the virus. Tissue and cellular specific ISH signal were recorded and semi-quantitatively graded using light microscopy. Positive hybridization signal for EEHV1A terminase and DNA polymerase was detected in tissues from all twelve study cases. In all tissues, positive signal was limited to endothelial cell nuclei. No signal was detected in epithelial cells, leukocytes or mesenchymal cells other than endothelial cells. Signal detection frequency was as follows: heart (12/12), liver (11/12), tongue (10/12), lymph node (10/12), spleen (9/11), stomach (9/12), small intestine (9/10), large intestine (9/10), lung (7/10), salivary gland (1/8), kidney (1/12), brain/spinal cord (0/10). Tissue signal amount varied among cases but generally was most abundant in heart and liver. Results confirmed that in Asian elephant cases of EEHV1A-HD, the viral cellular target and site of replication is exclusively capillary endothelial cells. Differences in viral tissue tropism with EEHV1A-HD are likely a consequence of endothelial cell heterogeneity across tissues. Understanding tropism in cases of active EEHV-HD can serve as a foundation for investigation of EEHV tropism in other stages of the infection (e.g. initial infection, dissemination, latency, shedding) and contribute to defining pathogenesis.

    Keywords

    Animals, Elephants, Herpesviridae Infections, Viral Tropism, Herpesviridae, In Situ Hybridization, Male

    Published Open-Access

    yes

    Share

    COinS
     
     

    To view the content in your browser, please download Adobe Reader or, alternately,
    you may Download the file to your hard drive.

    NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.