Roles of the auxiliary genes and AP-1 binding site in the long terminal repeat of feline immunodeficiency virus in the early stage of infection in cats.
To examine the roles of auxiliary genes and the AP-1 binding site in the long terminal repeat of feline immunodeficiency virus (FIV) in vivo, three mutant viruses, which are defective in the vif gene ([delta]vif), ORF-A gene (deltaORF-A), and AP-1 binding site (deltaAP-1), and wild-type virus as a positive control were separately inoculated into three specific-pathogen-free cats. These cats were assessed by measuring the number of proviral DNA copies in peripheral blood mononuclear cells (PBMCs), the CD4/CD8 ratio and antibody responses to FIV for 16 weeks and then examining histological changes at necropsy. Although viral DNAs were detected in PBMCs from all 12 cats to various degrees until 16 weeks postinoculation, no virus was recovered from PBMCs of cats infected with (delta)vif virus during the observation period. However, a very weak antibody response was induced in one cat infected with the (delta)vif virus. In contrast, despite the successful recovery of virus from both groups of cats infected with deltaORF-A and deltaAP-1 virus, antibody responses and decrease in the CD4/CD8 ratio in the groups were milder than those in cats infected with wild-type virus. Furthermore, the numbers of proviral DNA copies in PBMCs from the two groups were not able to reach the level in cats infected with wild-type virus during the observation period. From these results, we conclude that these mutant viruses are still infectious for cats but failed in efficient viral replication and suggest that these auxiliary genes and enhancer element are important or essential to full viral replication kinetics and presumably to full pathogenicity during the early stage of infection in vivo.
Inoshima
Y
Y
Department of Veterinary Microbiology, Faculty of Agriculture, The University of Tokyo, Bunkyo-ku, Japan.
Kohmoto
M
M
Ikeda
Y
Y
Yamada
H
H
Kawaguchi
Y
Y
Tomonaga
K
K
Miyazawa
T
T
Kai
C
C
Umemura
T
T
Mikami
T
T
D000818:Animals; D001665:Binding Sites; D016516:CD4-CD8 Ratio; D002415:Cats; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D015683:Gene Products, gag; D016341:Genes, vif / Q000235:genetics / Q000276:immunology*; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007963:Leukocytes, Mononuclear / Q000821:virology; D009500:Neutralization Tests; D012091:Repetitive Sequences, Nucleic Acid; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D004279:DNA, Viral; D015683:Gene Products, gag; D018808:Transcription Factor AP-1