QUASI-SPECIES EVOLUTION OF A HYPERVARIABLE REGION OF THE FELINE CALICIVIRUS CAPSID GENE IN CELL-CULTURE AND IN PERSISTENTLY INFECTED CATS

Feline calicivirus (FCV) is a respiratory pathogen of cats that is cap able of causing persistent infections. This study examined the evoluti on of a hypervariable region of the FCV capsid gene both during 90 pas sages in cell culture and during replication in persistently infected cats. This region of the capsid protein is known to contain neutraliza tion epitopes and may be a target for immune evasion during virus pers istence in the host. Sequence analysis showed that FCV exists as a qua sispecies which evolved both in cell culture and in persistently infec ted cats. Changes involved both loss of sequence present in the infect ing isolate and a gain of both synonymous and non-synonymous nucleotid e substitutions to generate sequences not detected within earlier isol ates. Overall, these changes led to a reduction in population heteroge neity over time. Where virus populations were highly homogeneous allow ing a consensus sequence to be determined, evolution rates for the con sensus sequence ranged from 0.10-1.07 substitutions per nucleotide per year. Marked changes in virus neutralization profiles were seen in is olates obtained sequentially from a persistently infected cat. This wa s not the case with cell culture passaged virus, suggesting that the i ndividual amino acid changes found only in virus from persistently inf ected cats may significantly alter the antigenic profile of FCV, and m ay be the result of immune selection.