Expanded host cell tropism and cytopathic properties of feline immunodeficiency virus strain PPR subsequent to passage through interleukin-2-independent T cells.

Abstract

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.

• Authors: D L Lerner, J H Elder
• Journal: Journal of virology (J Virol) Vol. 74 Issue 4 Pg. 1854-63 (Feb 2000) ISSN: 0022-538X [Print] United States
• PMID: 10644358 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokine CCL4
• Chemokine CCL5
• Interleukin-2
• Macrophage Inflammatory Proteins

Topics

• Amino Acid Sequence
• Animals
• Cats
• Cell Line
• Chemokine CCL4
• Chemokine CCL5 (pharmacology)
• Cytopathogenic Effect, Viral
• Giant Cells
• Immunodeficiency Virus, Feline (physiology)
• Interleukin-2 (physiology)
• Macrophage Inflammatory Proteins (pharmacology)
• Molecular Sequence Data
• Mutation
• T-Lymphocytes (drug effects, virology)
• Transfection
• Tropism