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Published 1984 | public
Journal Article

Complete Nucleotide Sequence of the Genomic RNA of Sindbis Virus


The entire nucleotide sequence of the genomic RNA of the type virus of the alphavirus genus, Sindbis virus, has been determined. The genome is 11,703 nucleotides in length, exclusive of the 5' cap and the 3'-terminal poly(A) tract. After the 5'-terminal cap there are 59 nucleotides of 5' nontranslated nucleic acid followed by a reading frame of 7539 nucleotides that encodes the nonstructural polypeptides and which is open except for a single opal termination codon. Following 48 untranslated bases located in the junction region which separates the nonstructural and structural protein coding sequences, there is an open reading frame 3735 nucleotides long that encodes the structural proteins. Finally, the 3' untranslated region is 322 nucleotides long. The nonstructural proteins are translated from the genomic RNA as two polyprotein precursors. The first is 1896 amino acids in length and terminates at an opal codon at position 1897. This polyprotein is processed to produce three polypeptides called nsPl, nsP2, and nsP3. Sites of post-translational cleavage to produce these three proteins have been tentatively located using available N-terminal amino acid sequence data. In both cases cleavage probably occurs between the two alanine residues in the sequence Gly-Ala-Ala. The fourth nonstructural protein, nsP4, is produced when readthrough of the opal codon produces a second polyprotein precursor of length 2513 amino acids, which is also cleaved posttranslationally. The structural proteins are translated from a subgenomic message which begins at nucleotide 7598, is 4106 nucleotides in length (exclusive of the poly(A) tract), and is coterminal with the 3' end of the genomic RNA. The structural proteins are also translated as a polyprotein precursor which is cleaved to produce a nucleocapsid protein and two integral membrane glycoproteins as well as two small peptides not present in the mature virion. A replication strategy for Sindbis virus based upon the complete nucleotide sequence, as well as prior data, is presented.

Additional Information

© 1984 Academic Press, Inc. Received September 20, 1983; accepted November 17, 1983. S. Maeda and C. Arias participated in the early stages of this project and we are grateful for their help and inspiration. J. Ou prepared some of the fragments used for sequencing, and E. Lenches furnished excellent technical assistance in preparation of cells and virus. T. Hunkapiller wrote the computer programs used in handling of the nucleotide sequences and preparation of the figures and we are grateful to him for access to these programs and instruction in their use, and to L. Hood for use of the computer facilities. This work was supported by Grants AI 10793 and GM 06965 from the National Institutes of Health and by Grant PCM 8022830 from the National Science Foundation.

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October 18, 2023