Development of feline immunodeficiency virus ORF-A (tat) mutants: in vitro and in vivo characterization.
A functional ORF-A is essential for efficient feline immunodeficiency virus replication in lymphocytes. We have characterized a series of mutants of the Petaluma strain, derived from p34TF10 and having different combinations of stop codons and increasingly long deletions in ORF-A. Six clones proved fully replicative in fibroblastoid Crandell feline kidney cells and monocyte-derived macrophage cultures but failed to replicate in T cell lines and primary lymphoblasts. Cats inoculated with three selected mutants had considerably milder infections than controls given intact ORF-A virus. In vivo, the mutants maintained growth properties similar to those in vitro for at least 7 months, except that replication in lymphoid cells was strongly reduced but not ablated. One mutant underwent extensive ORF-A changes without, however, reverting to wild-type. Antiviral immune responses were feeble in all cats, suggesting that viral loads were too low to represent a sufficiently powerful antigenic stimulus.
Pistello
M
M
Retrovirus Center and Virology Section, University of Pisa, Italy. pistello@biomed.unip.it
Moscardini
M
M
Mazzetti
P
P
Bonci
F
F
Zaccaro
L
L
Isola
P
P
Freer
G
G
Specter
S
S
Matteucci
D
D
Bendinelli
M
M
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000235:genetics*; D036022:Capsid Proteins; D002415:Cats; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016180:Lentivirus Infections / Q000276:immunology / Q000821:virology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000821:virology*; D009154:Mutation; D013601:T-Lymphocytes / Q000821:virology; D014766:Viremia; D014779:Virus Replication
D000914:Antibodies, Viral; D036022:Capsid Proteins; D006023:Glycoproteins