Published on 14 January 2025

Ewe-to-Lamb Transmission of Wesselsbron Virus: A Neglected Flavivirus in Focus

Wesselsbron virus (WSLV) is a neglected mosquito-borne zoonotic pathogen endemic to Sub-Saharan Africa. This study reveals a previously unknown mode of transmission of WSLV from lactating ewes to their lambs, highlighting an unrecognized risk for public and animal health associated with consumption of raw milk products. It also shows for the first time that strains of WSLV have different tropisms for the liver or brain.

• Why is this study important?

  Orthoflaviviruses are a large family of viruses that cause severe diseases transmitted by arthropod vectors, such as ticks (e.g., tick-borne encephalitis virus) and mosquitoes (e.g., yellow fever virus). Climate change and human activities have expanded the geographical distribution of these vectors and the pathogens they carry. Recent unforeseen epidemics of Zika virus worldwide, Japanese Encephalitis virus in India and Australia, and West Nile virus in Europe and North America exemplify the emergence of diseases in new regions with immunologically naïve populations, where these viruses can spread efficiently. Most pandemics also result from spillover events of largely uncharacterized viruses from animals to humans, and some Orthoflaviviruses can be transmitted through direct contact with infected individuals.

  This study focused on WSLV, a neglected Orthoflavivirus known for causing abortions and stillbirths in small ruminants and for being transmitted by Aedes (tiger) mosquitoes. WSLV also infects humans, but the reported cases were mostly associated with accidental exposure to contaminated samples. Symptoms were generally mild to moderate fever with headache and muscle pain, but encephalitis was also reported. It is likely that disease caused by WSLV is underdiagnosed because its symptoms are hard to distinguish from those of yellow fever or dengue in humans, or Rift Valley fever in ruminants.

  This study brings a new level of understanding of the transmission mechanisms and pathogenicity of WSLV and underscores the need for more research to enhance preparedness against neglected viruses with zoonotic potential.

• Description of the study

  The study was led by Dr Obdulio García-Nicolás and Prof. Charaf Benarafa, in a project funded by the Multidisciplinary Center for Infectious Diseases (MCID) at the University of Bern. First identified in South Africa in the 1950s, WSLV is now endemic to Sub-Saharan Africa, but only few virus isolates are available for research and none are contemporary. To address this gap, a reverse genetics method was used to generate a recombinant clade I WSLV strain (rSA999), through transformation-associated recombination (TAR) cloning in yeast.

  We then investigated the pathogenicity and transmission of the rSA999 strain compared to the clade II strain (SAH177) in sheep at the. biocontainment facilities of the IVI, and showed that both strains were equally transmitted from infected ewes to their suckling lambs at a rate of 40%. Clinical manifestations, viremia, and viral loads in the milk and other bodily fluids were measured in the ewes and their lambs. Disease symptoms and the different tissue tropisms of the viral strains were further validated by histopathological examinations and blood biochemistry analyses. Neutralizing antibody responses were quantified to assess the immune responses established in the infected animals.

• What are the main findings?

  • Adult sheep infected with both WSLV strains developed clinical signs of disease, including fever and reduced milk production, which reduced the growth of the lambs.
  • Elevated viral loads in the blood were followed by virus secretion in bodily fluids, with particularly elevated concentrations in nasal secretions and milk..
  • The ewes with higher viral titers in their milk transmitted the infection to their lambs, which developed fever and prolonged viremia.
  • The animals infected with the WSLV clade I strain (rSA999) had more pronounced liver damage than those infected with the clade II strain (SAH177). In contrast, brain lesions consistent with meningoencephalitis were only found in animals infected with the SAH177 strain, indicating a strain-specific tropism.
  • All animals that recovered from the infection developed very high levels of protective antibodies capable of preventing infection by either WSLV strain in vitro. This raises the hope that vaccination against one strain of WSLV might protect against multiple strains.

• Next step

  A direct follow-up to this study is to test other potential mechanisms of direct transmission of WSLV, in addition to milk. In terms of immunity against WSLV, further work should establish the relative importance of antibodies and T cell responses against infection. Regarding epidemiology and diagnostics, recent studies have identified the presence of WSLV in mosquitoes and rodents in East and West Africa, which suggests that further surveys are needed to identify the geographic distribution of the virus in insects and further define reservoir hosts in urban areas.

Title and link (Plos Pathogens)
Mosquito-independent milk-associated transmission of zoonotic Wesselsbron virus in sheep

Authors
Marta Zimoch, Llorenç Grau-Roma, Matthias Liniger, Noelle Donzé, Aurélie Godel, Damián Escribano, Bettina Salome Trüeb, Paraskevi Pramateftaki, Sergi Torres-Puig, José Joaquín Cerón, Volker Thiel, Jörg Jores, Artur Summerfield, Nicolas Ruggli, Charaf Benarafa, Obdulio García-Nicolás