Scientists in China have identified a novel tick-borne virus that causes an influenza-like illness characterized by fever, fatigue, gastrointestinal (GI) symptoms, and abnormal lab findings.

The team, led by researchers from the State Key Laboratory of Pathogen and Biosecurity in Beijing, has designated the new orthonairovirus as the Asian longhorned tick nairovirus (ALTNV).

Their discovery, published yesterday in the New England Journal of Medicine, stemmed from a probe into why 30% of patients with signs and symptoms of infection with Dabie bandavirus (DBV) test negative for the tick-borne hemorrhagic fever.

Distribution and Characteristics of Asian Longhorned Tick Nairovirus (ALTNV)

Panel A shows the geographic distribution of ticks and patients infected with ALTNV. The table shows areas where ticks were sampled and the prevalence of ALTNV RNA positivity among sampled ticks, and the map shows areas with patients who were positive for ALTNV RNA. In the map, circles indicate the locations of patients who were positive for ALTNV RNA; circle size is proportional to the number of positive patients. Panel B shows the results of a phylogenetic analysis of ALTNV. The tree was constructed on the basis of the complete amino acid sequence of RNA-directed RNA polymerase (the L protein). Recognized species in the family Nairoviridae were included in the analysis. ALTNV was obtained from humans, questing ticks, and feeding ticks in this study. The scale bar denotes the number of nucleotide substitutions per site. CCHFV denotes Crimean–Congo hemorrhagic fever virus. Panel C shows uninfected and ALTNV-infected Vero cells detected on immunofluorescence assay. The infected Vero cells had been inoculated with a serum sample obtained from a patient with ALTNV infection. Panel D shows negatively stained virions purified from ALTNV-infected Vero cells (top) and an image obtained on transmission electron microscopy of ALTNV-infected Vero cells (bottom, arrows).

Severe fever, low platelet count

DBV disease, which causes severe fever with thrombocytopenia syndrome (SFTS), is found throughout Asia and has a case-fatality rate of 10% to 30%. Thrombocytopenia is a low platelet count. The World Health Organization lists DBV as a priority for research.

The team obtained samples from patients bitten by ticks at sentinel hospitals in parts of China where tick-borne viruses circulate. The researchers identified the new virus through RNA sequencing and viral isolation.

The cocirculation of ALTNV and DBV in the same areas, coupled with their shared tick vector, underscores the need for improved differential diagnosis between infections with these viruses in regions where SFTS is endemic.

Phylogenomic analyses identified ALTNV as an orthonairovirus in the family Nairoviridae that shared under 80% of the amino acids in other species in the genus.

Inoculation of cells with ALTNV RNA–positive human serum resulted in growth of a virus identified via immunofluorescence of viral antigen as ALTNV. Characteristics of orthonairoviruses were also seen on electron microscopy, and viral replication was detected in multiple cell lines.

15% of DBV-negative patients had ALTNV

Of all 3,163 patients tested, 10.4% were positive for ALTNV based on detection of RNA or immunoglobulin M antibodies. Among patients who tested negative for DBV, 15.1% tested positive for ALTNV.

The most common manifestations of infection with ALTNV alone were fatigue (84%), GI problems (80%), thrombocytopenia (38%), and elevated aminotransferase concentrations (indicating inflammation or injury of the liver or other tissues; 36%). These patients recovered completely.

Relative to infection with DBV alone, coinfection with ALTNV and DBV (38 patients) was linked to higher rates of respiratory symptoms (61% vs 38%) and kidney impairment (84% vs 66%). Seven (18.4%) coinfected patients died.

ALTNV RNA was detected in 1.3% of 47,428 ticks in 15 provinces, with the highest prevalence in Haemaphysalis longicornis ticks (1.8%). Experiments showed that H longicornis can transmit the virus to mice.

“The cocirculation of ALTNV and DBV in the same areas, coupled with their shared tick vector, underscores the need for improved differential diagnosis between infections with these viruses in regions where SFTS is endemic,” the authors concluded.

Source – The University of Minnesota