COMPLETION OF THE TULA HANTAVIRUS GENOME SEQUENCE - PROPERTIES OF THEL-SEGMENT AND HETEROGENEITY FOUND IN THE 3' TERMINI OF S-GENOME AND L-GENOME RNAS

In this study the L segment and the 5' and 3' termini of the S, M and L segments of the prototype Tula hantavirus (TUL) were sequenced, thus completing the first determination of the genome sequence of a hantav irus that has not been linked to any human disease. The TUL L segment comprises 6541 nt with one ORF of 6459 nt in the antigenome sense. Thi s ORF potentially encodes a 2153 aa protein with a predicted molecular mass of 247 kDa, The amino acid sequence includes all the motifs cons erved in RNA-dependent RNA polymerases. The 5' termini of all three ge nome RNAs (vRNAs) had the expected sequences conserved in hantaviruses . The 3' termini of M vRNAs were also conserved. However, the 3' termi ni of S and L vRNAs were heterogeneous as most of the sequenced 3' ter mini had either deletions of 1 to 22 nt or an extra 1 to 3 nt. No incr ease in the level of heterogeneity was seen in vRNAs of virions collec ted 3, 6, 9 and 12 days postinfection, suggesting that the heterogenei ty already exists at the early stages of infection. The S and L vRNAs from infected cells had more truncated 3' termini than vRNAs from pell eted virus. Heterogeneity of the 3' termini of genome RNAs could decre ase the efficiency of antigenome and mRNA syntheses and contribute to the slow growth observed for TUL and other hantaviruses in cell cultur e.