09-10-2021-2043 - Complete genome sequence of Montana Myotis leukoencephalitis virus, phylogenetic analysis and comparative study of the 3' untranslated region of flaviviruses with no known vector

Comparative Study  J Gen Virol

. 2002 Aug;83(Pt 8):1875-1885. doi: 10.1099/0022-1317-83-8-1875.

Complete genome sequence of Montana Myotis leukoencephalitis virus, phylogenetic analysis and comparative study of the 3' untranslated region of flaviviruses with no known vector

Nathalie Charlier  1 , Pieter Leyssen  1 , Cornelis W A Pleij  2 , Philippe Lemey  1 , Frédérique Billoir  3 , Kristel Van Laethem  1 , Anne-Mieke Vandamme  1 , Erik De Clercq  1 , Xavier de Lamballerie  3 , Johan Neyts  1

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PMID: 12124451  DOI: 10.1099/0022-1317-83-8-1875

 Montana Myotis leukoencephalitis virus (MMLV), a virus isolated from bats, causes an encephalitis in small rodents reminiscent of flavivirus encephalitis in humans. The complete MMLV genome is 10690 nucleotides long and encodes a putative polyprotein of 3374 amino acids.

https://pubmed.ncbi.nlm.nih.gov/12124451/

JOURNAL OF GENERAL VIROLOGY Volume 83, Issue 8

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Complete genome sequence of Montana Myotis leukoencephalitis virus, phylogenetic analysis and comparative study of the 3′ untranslated region of flaviviruses with no known vector Free

Nathalie Charlier1, Pieter Leyssen1, Cornelis W. A. Pleij2, Philippe Lemey1, Frédérique Billoir3, Kristel Van Laethem1, Anne-Mieke Vandamme1, Erik De Clercq1, Xavier de Lamballerie3, Johan Neyts1

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First Published: 01 August 2002  

Montana Myotis leukoencephalitis virus (MMLV), a virus isolated from bats, causes an encephalitis in small rodents reminiscent of flavivirus encephalitis in humans. The complete MMLV genome is 10690 nucleotides long and encodes a putative polyprotein of 3374 amino acids. The virus contains the same conserved motifs in genes that are believed to be interesting antiviral targets (NTPase/helicase, serine protease and RNA-dependent RNA polymerase) as flaviviruses of clinical importance. Phylogenetic analysis of the entire coding region has confirmed the classification of MMLV in the clade of the flaviviruses with no known vector (NKV) and within this clade to the Rio Bravo branch (both viruses have the bat as their vertebrate host). We have provided for the first time a comparative analysis of the RNA folding of the 3′ UTR of the NKV flaviviruses (Modoc, Rio Bravo and Apoi viruses, in addition to MMLV). Structural elements in the 3′ UTR that are preserved among other flaviviruses have been revealed, as well as elements that distinguish the NKV from the mosquito- and tick-borne flaviviruses. In particular, the pentanucleotide sequence 5′ CACAG 3′, which is conserved in all mosquito- and tick-borne flaviviruses, is replaced by the sequence 5′ C(C/U)(C/U)AG 3′ in the loop of the 3′ long stable hairpin structure of all four NKV flaviviruses. The availability of this latter sequence motif allows us to designate a virus as either an NKV or a vector-borne flavivirus.

flaviviruses with no known arthropod vector (NKV) 

Virus.The original MMLV strain (Montana, 1958) was obtained from the ATCC (ATCC VR-537) and grown in Vero cells.

Five of the flavivirus polyprotein cleavages take place after two basic amino acids (either Lys–Arg or Arg–Arg or Arg–Lys) (Chambers et al., 1990R7 ): i.e. anchored C–virion C, NS2A–NS2B, NS2B–NS3, NS3–NS4A and NS4B–NS5. In the case of MMLV, an Arg–Arg sequence is present at the C-termini of NS2B, NS3 and NS4B. In the case of MMLV, an Arg–Arg sequence is present at the C-termini of NS2B, NS3 and NS4B. For the other two cleavages (anchored C–virion C and NS2A–NS2B), suitable dibasic sequences could not be identified. 

The ORF of the flavivirus genome is flanked by short non-coding regions, which may contain elements involved in the regulation of essential functions such as translation, replication or encapsidation of the genome (Cammisa-Parks et al., 1992R6 ).

Table 2. Predicted protease cleavage sites in MMLV as compared with another NKV virus (RBV), a mosquito-borne virus (YFV) and a tick-borne virus (TBEV)

The flavivirus NS5 protein (the largest of the flavivirus-encoded proteins) encodes an RNA-dependent RNA polymerase and also contains a putative methyltransferase domain (Koonin, 1993R20 ).

The deduced amino acid sequence of MMLV revealed conservation of the main features of flaviviruses, i.e. cleavage and glycosylation sites of virus-specific proteins, and the presence of highly conserved motifs important for protease, helicase, methyltransferase and RNA-dependent RNA polymerase activity (Monath & Heinz, 1996R28 ). 

It was suggested that the variable region could possibly act as a spacer separating the folded 3′ UTR structure from the rest of the genome (Blackwell & Brinton, 1995R3 ). 

The phylogenetic tree based on the UTRs of NKV flaviviruses showed similar topology to those constructed from the coding regions (data not shown), indicating that the genetic information in these regions reflects the evolutionary history of MMLV and the other NKV flaviviruses. 

APOIV is the most distantly positioned flavivirus within the NKV flavivirus cluster. The particular characteristics of the secondary structure of the 3′ UTR of APOIV (absence of region I and presence of a duplicated region II) corroborates this observation. Interestingly, MMLV and RBV, which both have the bat as their natural host, share a common pseudoknot structure (located between regions I and II). Moreover, the sequence of region I in the 3′ UTR of MMLV and RBV is very similar, whereas the stems contain compensatory mutations.

https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-83-8-1875