Extensive sequence variation of feline immunodeficiency virusenv genes in isolates from naturally infected cats

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Abstract
Summary In an investigation of the evolution of feline immunodeficiency virus (FIV) in vivo, sequential isolates from a persistently infected cat were examined by direct sequencing following amplification of selected subgenomic regions by polymerase chain reaction (PCR). Three isolates, T 90, T 91, and T 92, obtained over a three-year period revealed no changes to regions known to be conserved withingag andpol genes. Additionally, no change occurred withingag andpol in an isolate recovered from a second cat which was experimentally infected with T 90. Changes were detected within an N-terminal region of the envelope glycoprotein gp 120 (env). These consisted of point mutations, some of which would result in amino acid substitutions and the predicted amino acid changes tended to cluster within variable domains. Inoculation of T 90 into a second cat resulted in a different pattern of mutations than that observed for the three isolates from the first cat. In all cases, virus isolates derived from the same cat were much more highly related to each other (extent ofenv variation was 0.5–1.5%) than to isolates from other cats (10–12%env variation). The rate of change of FIV was estimated to be 3.4×10−3 nucleotide substitutions per site per year for theenv gene and less than 10−4 nucleotide substitutions per site per year for thegag andpol genes, values concordant with that found for human immunodeficiency virus 1. Both nucleotide and amino acid changes in the gp 120 region were found to be directional, suggesting that selective pressures influence FIV envelope gene sequences.