Persistence of viral full-length genomic RNA and replication-associated RNA transcripts and proteins in sheep tissues following acute Crimean-Congo hemorrhagic fever virus infection
- 1National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada
- 2Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne RNA virus responsible for a severe hemorrhagic disease in humans. In contrast, the virus appears to cause only a brief viremia without overt clinical signs in animals such as livestock, following which the infection is traditionally assumed to end with complete viral clearance. Here, we challenge this prevailing view by reporting the recovery of full-length viral genomic RNA sequences from tissues of CCHFV-infected sheep long after the resolution of acute viremia. While viral RNA persistence in these tissues was largely characterized by a lack of extensive viral replication, we detected the sporadic presence of replication-associated viral RNA transcripts and viral proteins. These findings suggest that the biology of CCHFV in animals extends well beyond an acute infection. The possibility that the virus can transition into a dormant state, with potential for reactivation to resume gene expression or replication, a phenomenon documented in other RNA viruses, warrants further investigation. Author summary: Crimean–Congo hemorrhagic fever virus (CCHFV) is a tick‑borne virus that can cause a dangerous bleeding disease in humans. Livestock can also become infected and contribute to viral spread while showing no signs of illness. Traditionally, infected animals are believed to experience only a short period (a few days) of viral presence in their blood, after which the virus is thought to be completely cleared, leaving no viral footprint in the body. Our study challenges this long‑held assumption. In experimentally infected sheep, we found that intact CCHFV genetic material remains in lymphoid tissues weeks after the brief infection in the bloodstream has ended. This occurs without extensive production of infectious virus, while rare traces of viral RNA or protein associated with replication activities can still be found. These features suggest that the virus enters a predominantly silent, dormant‑like state possibly with potential for reactivation, rather than being fully eliminated. Our findings reveal that CCHFV can establish an extended, hidden phase of infection in livestock, which may influence how the virus is maintained and transmitted.
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BibTeX
@article{li2026persistence,
title = {{Persistence of viral full-length genomic RNA and replication-associated RNA transcripts and proteins in sheep tissues following acute Crimean-Congo hemorrhagic fever virus infection}},
author = {Hongzhao Li and Estella Moffat and Katherine Handel and Michelle Nebroski and Daniel Sullivan and Andre Dufresne and Carissa Embury-Hyatt and Oliver Lung and Bradley S. Pickering},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = oct,
doi = {10.1371/journal.pntd.0014842},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014842},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Persistence of viral full-length genomic RNA and replication-associated RNA transcripts and proteins in sheep tissues following acute Crimean-Congo hemorrhagic fever virus infection
AU - Hongzhao Li
AU - Estella Moffat
AU - Katherine Handel
AU - Michelle Nebroski
AU - Daniel Sullivan
AU - Andre Dufresne
AU - Carissa Embury-Hyatt
AU - Oliver Lung
AU - Bradley S. Pickering
PY - 2026
DA - 2026/10/30
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014842
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014842
AB - Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne RNA virus responsible for a severe hemorrhagic disease in humans. In contrast, the virus appears to cause only a brief viremia without overt clinical signs in animals such as livestock, following which the infection is traditionally assumed to end with complete viral clearance. Here, we challenge this prevailing view by reporting the recovery of full-length viral genomic RNA sequences from tissues of CCHFV-infected sheep long after the resolution of acute viremia. While viral RNA persistence in these tissues was largely characterized by a lack of extensive viral replication, we detected the sporadic presence of replication-associated viral RNA transcripts and viral proteins. These findings suggest that the biology of CCHFV in animals extends well beyond an acute infection. The possibility that the virus can transition into a dormant state, with potential for reactivation to resume gene expression or replication, a phenomenon documented in other RNA viruses, warrants further investigation. Author summary: Crimean–Congo hemorrhagic fever virus (CCHFV) is a tick‑borne virus that can cause a dangerous bleeding disease in humans. Livestock can also become infected and contribute to viral spread while showing no signs of illness. Traditionally, infected animals are believed to experience only a short period (a few days) of viral presence in their blood, after which the virus is thought to be completely cleared, leaving no viral footprint in the body. Our study challenges this long‑held assumption. In experimentally infected sheep, we found that intact CCHFV genetic material remains in lymphoid tissues weeks after the brief infection in the bloodstream has ended. This occurs without extensive production of infectious virus, while rare traces of viral RNA or protein associated with replication activities can still be found. These features suggest that the virus enters a predominantly silent, dormant‑like state possibly with potential for reactivation, rather than being fully eliminated. Our findings reveal that CCHFV can establish an extended, hidden phase of infection in livestock, which may influence how the virus is maintained and transmitted.
SN - 1935-2735
SN - 1935-2727
ER -