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Localization of Genomic Regions Specific for the Attenuated, Mouse-adapted Poliovirus Type 2 Strain W-2

Daniel C. Pevear

Chad K. Oh^>

Burk Jubelt

The Les Turner ALS Research Laboratory, Department of Neurology, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, Illinois 60611, U.S.A.

In order to begin to elucidate the genomic basis of the attenuation of mouse-adapted, poliovirus type 2 strain W-2 (PV2/W-2), we have cloned and sequenced the virus and compared it with the virulent, mouse-adapted PV2/Lansing strain. In addition, we have performed computer-generated comparisons of PV2/W-2 to the non-mouse-adapted, attenuated PV2/Sabin strain to determine whether mutational patterns occur that result in attenuation. The PV2/W-2 genome is 7434 nucleotides in length, which is three bases shorter than PV2/Lansing. The 5' non-coding region of PV2/W-2 is 747 nucleotides in length (compared to 744 in PV2/Lansing) and shares 98·8% identity with PV2/Lansing and 82.3% identity with PV2/Sabin. Overall, the PV2/W-2 polyprotein (2205 amino acids) is two amino acids shorter than that of either PV2/Lansing or PV2/Sabin (2207 amino acids). These contiguous deletions fall within the P3-D region (polymerase). Within these 2205 amino acid residues only 26 differences were observed between PV2/W-2 and PV2/Lansing (98·8% identity), whereas 92 occurred between PV2/W-2 and PV2/Sabin (95·8% identity). The 3' non-coding region of PV2/W-2 is 72 nucleotides in length and shares 100% identity with PV2/Lansing and 98·6% identity with PV2/Sabin. Amino acid changes in the capsid protein region occurred in neutralization sites 1 and 3, areas previously shown to be important for pathogenicity. The cleavage site between non-structural proteins P2-C/P3-A consisted of a glutamine-serine pair, in contrast to other sequenced polioviruses which have a glutamine-glycine dipeptide.

Present address: Sterling Drug Incorporated, Rensselaer, New York, U.S.A.

^> Present address: Department of Pediatrics, Rush-Presbyterian-St Luke's Hospital, Chicago, Illinois, U.S.A.

Present address: Department of Neurology, SUNY Health Science Center, 750 East Adams St, Syracuse, New York 13210, U.S.A.

Received 28 July 1989; accepted 26 September 1989.

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