Scientists in China have discovered a previously unknown tick-borne virus that can cause a flu-like illness involving fever, fatigue, gastrointestinal (GI) symptoms and unusual laboratory results.
Researchers led by the Beijing State Key Laboratory of Pathogens and Biosafety have named the newly identified ortonairvirus Asian longhorned tick nairovirus (ALTNV).
The discovery, reported in the New England Journal of Medicinearose from efforts to understand why about 30% of patients with symptoms suggestive of Dabie bandavirus (DBV) infection test negative for tick-borne hemorrhagic fever.
A search for the cause of unexplained tick illness
DBV causes severe fever with thrombocytopenia syndrome (SFTS), a life-threatening illness found throughout Asia. The infection has a case fatality rate of 10% to 30%. Thrombocytopenia refers to an abnormally low level of platelets, the blood cells involved in clotting. The World Health Organization has identified DBV as a priority pathogen for research.
To investigate unexplained cases, researchers collected samples from people who had been bitten by ticks and were treated at sentinel hospitals in regions of China where tick-borne viruses are known to circulate. Using RNA sequencing and viral isolation, the team detected the previously unknown virus.
“The cocirculation of ALTNV and DBV in the same areas, together with their shared tick vector, underscores the need to improve the differential diagnosis between infections with these viruses in regions where SFTS is endemic.”
Genetic analyzes placed ALTNV within the genus orthonairovirus in the family Nairoviridae. Its proteins shared less than 80% of their amino acids with those of other species in the genus, supporting its identification as a distinct virus.
The researchers also exposed laboratory cells to human serum containing ALTNV RNA. The virus grew in the cells and was identified as ALTNV using immunofluorescence to detect viral antigens. Electron microscopy revealed typical features of ortonairviruses, while additional experiments demonstrated that the virus could replicate in several cell types.
ALTNV found in more than 10% of patients analyzed
Among 3,163 patients included in the study, 10.4% tested positive for ALTNV based on the presence of viral RNA or immunoglobulin M antibodies, which may indicate recent infection.
The proportion was even higher among people who tested negative for DBV. In that group, 15.1% were positive for ALTNV.
Among patients infected only with ALTNV, the most common symptom was fatigue, reported by 84%. Gastrointestinal (GI) problems occurred in 80%, while 38% developed thrombocytopenia. Elevated concentrations of aminotransferases were found in 36% (indicating inflammation or injury of the liver or other tissues; 36%). These patients eventually made a full recovery.
Co-infections linked to more serious complications
The researchers also identified 38 patients who were infected with both ALTNV and DBV.
Compared to people infected with DBV alone, those with both viruses experienced respiratory symptoms more frequently, affecting 61% compared to 38%. Kidney failure was also more common in co-infected patients, occurring in 84% compared to 66%.
Seven of the 38 co-infected patients died, representing 18.4% of that group.
Virus detected in ticks in 15 provinces
The researchers also tested 47,428 ticks collected in 15 provinces. ALTNV RNA was present in 1.3% of them.
The highest prevalence was found in Haemaphysalis longicorniscommonly known as the Asian longhorned tick, and 1.8% tested positive.
Laboratory experiments provided further evidence that this species of tick can transmit the virus. The researchers showed that H. longicornis was able to transmit ALTNV to mice.
Because ALTNV and DBV occur in the same regions and can be transmitted by the same tick vector, researchers say distinguishing between the two infections could become increasingly important.
“The cocirculation of ALTNV and DBV in the same areas, together with their shared tick vector, underscores the need to improve the differential diagnosis between infections with these viruses in regions where SFTS is endemic,” the authors concluded.