Charlier Nathalie, Leyssen Pieter, Pleij Cornelis W A, Lemey Philippe, Billoir Frédérique, Van Laethem Kristel, Vandamme Anne-Mieke, De Clercq Erik, de Lamballerie Xavier, Neyts Johan
Laboratory of Virology and Chemotherapy1 and Laboratory of Clinical and Epidemiological Virology2, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands3.
J Gen Virol. 2002 Aug;83(Pt 8):1875-1885. 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. 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.
蒙大拿州白鼻蝠脑炎病毒（MMLV）是一种从蝙蝠中分离出的病毒，可在小型啮齿动物中引发脑炎，类似于人类的黄病毒脑炎。MMLV的完整基因组长度为10690个核苷酸，编码一个由3374个氨基酸组成的推定多聚蛋白。该病毒在被认为是有趣的抗病毒靶点的基因（NTPase/解旋酶、丝氨酸蛋白酶和RNA依赖性RNA聚合酶）中含有与具有临床重要性的黄病毒相同的保守基序。对整个编码区的系统发育分析已证实MMLV在无已知载体的黄病毒进化枝（NKV）中，并且在该进化枝内属于里奥布拉沃分支（两种病毒都以蝙蝠作为脊椎动物宿主）。我们首次对NKV黄病毒（除MMLV外，还有莫多克病毒、里奥布拉沃病毒和阿波伊病毒）3'UTR的RNA折叠进行了比较分析。揭示了在其他黄病毒中保守的3'UTR结构元件，以及区分NKV与蚊媒和蜱媒黄病毒的元件。特别是，在所有蚊媒和蜱媒黄病毒中保守的五核苷酸序列5' CACAG 3'，在所有四种NKV黄病毒的3'长稳定发夹结构的环中被序列5' C(C/U)(C/U)AG 3'取代。后一种序列基序的存在使我们能够将一种病毒指定为NKV或载体传播的黄病毒。
