Expanded host cell tropism and cytopathic properties of feline immunodeficiency virus strain PPR subsequent to passage through interleukin-2-independent T cells.
A cytopathic variant of feline immunodeficiency virus (FIV) strain PPR emerged after passage of wild-type virus on an interleukin-2-independent cell line. The virus, termed FIV-PPRglial, displayed a phenotype markedly different from the parental virus, including the ability to productively infect previously refractory cell lines, induction of large syncytia, and accelerated kinetic properties. A chimeric molecular clone, FIV-PPRchim42, containing the FIV-PPRglial envelope within the backbone of FIV-PPR, exhibited all the characteristics of the FIV-PPRglial phenotype, demonstrating that the viral envelope was responsible for the acquired traits. Subsequent molecular characterization revealed that the FIV-PPRglial envelope contained five amino acid substitutions relative to wild-type FIV-PPR. Mutagenic analyses further demonstrated that the acquired phenotype was minimally attributable to a combination of three mutations, specifically, a glutamine-to-proline change within the second constant domain of the surface protein (SU); a threonine-to-proline change within the V4 loop, also in the SU; and a premature stop codon in the cytoplasmic tail of the transmembrane protein. All three changes were required to produce the FIV-PPRglial phenotype. Cotransfection studies with mutant viruses in combination with each other and with FIV-PPR indicated that the truncated cytoplasmic tail was responsible for the induction of syncytium formation. Receptor usage analyses were pursued, and distinctions were observed between FIV-PPR and FIV-PPRglial. In vitro infections with FIV-PPR, FIV-PPRglial, and FIV-34TF10 on two adherent cell lines were ablated in the presence of SDF1alpha, the natural ligand for CXCR4. In contrast, viral infection of T cells was not limited to CXCR4 usage, and inhibition studies indicate the potential involvement of a CC chemokine receptor.
Lerner
D L
DL
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Elder
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D002460:Cell Line; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D015726:Giant Cells; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D014162:Transfection; D018523:Tropism
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins