Evolution of two amino acid positions governing broad neutralization resistance in a strain of feline immunodeficiency virus over 7 years of persistence in cats.
Fresh isolates of lentiviruses are characterized by an outstanding resistance to antibody-mediated neutralization. By investigating the changes that occurred in a neutralization-sensitive tissue culture-adapted strain of feline immunodeficiency virus after it was reinoculated into cats, a previous study had identified two amino acid positions of the surface glycoprotein (residues 481 and 557) which govern broad neutralization resistance (BNR) in this virus. By extending the follow-up of six independently evolving in vivo variants of such virus for up to 92 months, we now show that the changes at the two BNR-governing positions not only were remarkably stereotyped but also became fixed in an ordered sequential fashion with the duration of in vivo infection. In one variant, the two positions were also seen to slowly alternate at determining BNR. Evidence that evolution at the BNR-governing positions was accompanied, and possibly driven, by changes in the antigenic makeup of the viral surface brought about by the mutations at such positions is also presented.
Pistello
Mauro
M
Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, Pisa, Italy.
Matteucci
Donatella
D
Giannecchini
Simone
S
Bonci
Francesca
F
Sichi
Olimpia
O
Presciuttini
Silvano
S
Bendinelli
Mauro
M
D019943:Amino Acid Substitution; D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology; D002415:Cats; D004351:Drug Resistance / Q000235:genetics*; D019143:Evolution, Molecular; D016089:Immunodeficiency Virus, Feline / Q000235:genetics*; D016180:Lentivirus Infections / Q000821:virology; D009500:Neutralization Tests; D013997:Time Factors; D015678:Viral Structural Proteins / Q000235:genetics
D000914:Antibodies, Viral; D015678:Viral Structural Proteins