Construction and in vitro characterization of attenuated feline immunodeficiency virus long terminal repeat mutant viruses.
AP-1- and ATF-binding sites are cis-acting transcriptional elements within the U3 domain of the feline immunodeficiency virus (FIV) long terminal repeat (LTR) that serve as targets for cellular activation pathways and may regulate virus replication. We report that FIV LTR mutant proviruses encoding U3 deletions of the ATF-binding sequence exhibited restricted virus expression and replication in both feline lymphocytes and macrophages. In contrast, deletion of the AP-1 site had negligible effects on virus expression and replication. FIV LTR mutant proviruses encoding deletions of both the AP-1 and ATF sites or a 72-bp deletion encompassing the AP-1 site, duplicated C/EBP sites, and ATF sites were severely restricted for virus expression. These results demonstrate that deletion of either the ATF-binding site or multiple cis-acting transcriptional elements attenuates FIV. These attenuated FIV mutants provide opportunities to characterize the role of cis-acting elements in virus replication in vivo and to test LTR mutants as attenuated virus vaccines.
Bigornia
L
L
Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Lockridge
K M
KM
Sparger
E E
EE
D051696:Activating Transcription Factors; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D002415:Cats; D016089:Immunodeficiency Virus, Feline / Q000235:genetics* / Q000472:pathogenicity*; D008214:Lymphocytes / Q000821:virology; D008264:Macrophages / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011533:Proviruses / Q000235:genetics*; D017384:Sequence Deletion; D020079:Terminal Repeat Sequences / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014613:Vaccines, Attenuated; D014779:Virus Replication
D051696:Activating Transcription Factors; D001798:Blood Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014613:Vaccines, Attenuated