MOLECULAR ANALYSIS OF PUUMALA ORTHOHANTAVIRUS STRAINS IN HEMORRHAGIC FEVER WITH RENAL SYNDROME PATIENTS REVEAL GENOME VARIANTS UNIDENTIFIED IN BANK VOLE POPULATIONS

Abstract

Intro: Hemorrhagic fever with renal syndrome (HRFS) is endemic disease in the Republic of Tatarstan (RT). Infection is caused by Puumala orthohantavirus (PUUV) circulating in bank vole (Myodes glareolus) small rodents. However, knowledge on the connection between viruses identified in patients and bank voles is still limited in the RT. Establishing the link between virus strains in patients and bank voles could help to determine the site of infection. Methods: Total RNA was extracted from HFRS serum samples. The amplified PCR-products were obtained by RT-PCR using S and M segments specific primers and sequenced. Findings: PUUV RNA was detected in 88 out of 201 HFRS samples. The nucleotide sequences from 42 and 24 PUUV strains for S and M segments were obtained. Phylogenetic analysis had demonstrated that HFRS strains formed 7 (S segment) and 6 (M segment) groups. Most of these strain sequences matched sequences obtained from bank voles captured in the same area where patients presumably were infected. One PUUV strain detected in a patient infected in the Smak-Korsa village, contains the S segment from group G and the M segment from group D, suggesting that this strain is the result of reassortment. Discussion: Also, four reassortant genomes were identified in HFRS cases presumably infected near Vysokaya Gora village. Conclusion: These results suggest that the PUUV strain in HFRS patient would be similar to that circulating in bank voles which habitat in the same region. Therefore, by identifying PUUV genome in HFRS patients, virus distribution within the area and dissemination to other regions could be monitored. Also, reassortant PUUV strains were found exclusively in HFRS, while they were absent in bank voles. This study was supported by RFBR perspective grant 19-34-60012 and RSF-DST 22-44-02007 grant. Also, the Kazan Federal University Strategic Academic Leadership Program (PRIORITY-2030) funded this research.