Retention of viral infectivity after extensive mutation of the highly conserved immunodominant domain of the feline immunodeficiency virus envelope.
In lentiviruses, including human immunodeficiency virus and feline immunodeficiency virus (FIV), the principal immunodominant domain (PID) of the transmembrane glycoprotein elicits a strong humoral response in infected hosts. The PID is marked by the presence of two cysteines that delimit a sequence, composed of five to seven amino acids in different lentiviruses, which is highly conserved among isolates of the same lentiviral species. While the conservation of the sequence suggests the presence of functional constraints, the conservation of the immunodominance among divergent lentiviruses raises the hypothesis of a selective advantage for the infecting virus conferred by the host humoral response against this domain. We and others have previously shown that an appropriate structure of the PID is required for the production of a functional envelope. In the present work, we analyzed virological functions and immune reactivity of the envelope after random mutagenesis of the PID of FIV. We obtained nine mutant envelopes which were correctly processed and retained fusogenic ability. Mutation of the two C-terminal residues of the PID sequence between the cysteines in a molecular clone of FIV abolished infectivity. In contrast, three molecular clones containing extensive mutations in the four N-terminal amino acids were infectious. However, the mutations affected PID reactivity with sera from infected cats. Our results suggest that functional constraints, although existent, are not sufficient to account for PID sequence conservation. Such conservation may also result from positive selection by anti-PID antibodies which enhance infection.
Pancino
G
G
Génétique des Virus et Immunopharmacologie Moléculaire (ICGM-CNRS UPR0415), Institut Cochin de Génétique Moléculaire, Paris, France. pancino@cochin.inserm.fr
Sonigo
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D001667:Binding, Competitive; D002415:Cats; D004252:DNA Mutational Analysis; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015752:Genes, env; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013997:Time Factors; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D015686:Gene Products, env; D010455:Peptides; D014760:Viral Fusion Proteins; D012194:RNA-Directed DNA Polymerase