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Analysis of the Glycoprotein Gene of Tacaribe Virus and Neutralization-resistant Variants

Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, U.K.

We have previously generated neutralization-resistant variants of Tacaribe virus in the presence of a monoclonal antibody (MAb) specific for the envelope glycoprotein. The envelope glycoprotein precursor (GPC) genes of two variant viruses were sequenced following polymerase chain reaction amplification of a specific region of the Tacaribe virus S RNA, and compared with the GPC gene of the parental virus. Multiple nucleotide changes in the 3' half of the GPC gene were identified in the variants, suggesting that this part of the gene codes for the envelope glycoprotein of Tacaribe virus recognized by the MAb. Both variants showed unique amino acid substitutions up to 166 residues apart, suggesting that the most likely basis for neutralization resistance was a change in an epitope in which the critical residues are juxtaposed by conformation rather than by proximity in coding.

Received 13 March 1991; accepted 6 May 1991.